Publications by authors named "John R H Archer"

33 Publications

Acute toxicity related to misuse (nonmedical use) of tramadol: Experience of the European Drug Emergencies Network Plus.

Br J Clin Pharmacol 2021 04 15;87(4):1668-1675. Epub 2020 Jul 15.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro-DEN Plus database for the 4-year period from 1 January 2014 to 31 December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia; n = 11, 7.5% of all presentations to this centre), Riga (Latvia; n = 4, 4.9%) and Munich (Germany; n = 17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/Glasgow coma score ≤ 8 and 9 of these had a respiratory rate <12 breaths/min. These presentations potentially pose a significant burden on emergency departments with a large proportion requiring admission to hospital for ongoing care.
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http://dx.doi.org/10.1111/bcp.14408DOI Listing
April 2021

Establishing Reference Intervals for Gadolinium Concentrations in Blood, Plasma, and Urine in Individuals Not Previously Exposed to Gadolinium-Based Contrast Agents.

Invest Radiol 2020 07;55(7):405-411

Viapath Analytics, King's College Hospital NHS Foundation Trust, London, United Kingdom.

Objectives: Over the recent years, there have been increasing concerns that exposure to gadolinium-based contrast agents (GBCAs) may be associated with retention of Gd within the skin, bones, and solid organs in patients with normal renal function, although the clinical implications of this deposition remain to be established. There are no published data available to guide the development of reference intervals for Gd concentrations in biological samples from healthy people. The aims of this study were to (1) determine whether healthy individuals who have not received GBCAs have detectable concentrations of Gd in their blood and urine, and (2) to develop a reference range for Gd concentrations in blood and spot urine samples for healthy individuals.

Materials And Methods: Whole blood, plasma, and spot urine samples were taken from 120 healthy volunteers with estimated glomerular filtration rate 70 mL/min per 1.73 m or greater. Gd concentrations were measured in these samples using inductively coupled plasma mass-spectrometry. The reference intervals for Gd concentrations in whole blood, plasma, and urine were estimated as the 2.5th percentile and the upper reference limit as the 97.5th percentile.

Results: Ten (8.33%) of the 120 subjects had detectable concentrations of Gd in their whole blood (n = 5) or spot urine (n = 5) samples; no subjects had detectable concentrations of Gd in their plasma samples. Our proposed reference intervals for Gd are as follows: whole blood, <0.008 ng/mL or <0.050 nmol/L; plasma, <0.009 ng/mL or <0.057 nmol/L; spot urine, <0.036 μg/g or <0.0250 nmol/mmol.

Conclusions: The results of this study provide reference intervals for whole blood, plasma, and urine Gd concentrations in healthy subjects who have not previously received GBCAs and will assist clinicians in assessing patients who have concerns regarding potential Gd retention postexposure and help guide further clinical studies to explore the pharmacokinetics of GBCAs in patients with normal renal function.
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http://dx.doi.org/10.1097/RLI.0000000000000657DOI Listing
July 2020

Evaluation of long-term detection trends of new psychoactive substances in pooled urine from city street portable urinals (London, UK).

Br J Clin Pharmacol 2020 03 4;86(3):517-527. Epub 2020 Mar 4.

Department of Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Aims: To evaluate the long-term trends of new psychoactive substance (NPS) detection in pooled urine samples collected across a city centre.

Methods: Pooled urine samples from portable stand-alone urinals were collected on a monthly basis over 5.5 years (July 2013-December 2018) across a city centre. These were analysed using a high-performance liquid chromatography system, interfaced to a high-resolution accurate mass spectrometer. Data were processed against a database containing over 2000 drugs/metabolites including over 800 NPS.

Results: In total, 44 NPS were detected with variation over time including cathinones (15, 34.1%), synthetic cannabinoids (8, 18.2%) and 21 (47.7%) other NPS. Since the introduction of the UK Psychoactive Substances Act (May 2016) cathinone detection has decreased with minimal detection over the last 4 months of the study. Synthetic cannabinoids were not detected on a regular basis until July 2016 with a subsequent variable detection frequency. There was a consistent, low level detection frequency of all other NPS throughout the study, but which appears to have increased alongside the decrease in cathinone detection.

Conclusion: Pooled urine analysis of samples taken from portable urinals in a city centre can be used as an effective monitoring tool to determine long-term trends in the use of NPS. The results of this study demonstrate the impact of the Psychoactive Substances Act and reflect the findings of population surveys and clinical studies. Triangulation of these data with other data sources will enable greater insight into the NPS phenomenon.
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http://dx.doi.org/10.1111/bcp.14239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080623PMC
March 2020

Detection of cocaine and its metabolites in whole blood and plasma following a single dose, controlled administration of intranasal cocaine.

Drug Test Anal 2019 Sep 25;11(9):1419-1430. Epub 2019 Jul 25.

Analytical and Environmental Sciences Research Division, Faculty of Life Sciences and Medicine, King's College London, UK.

The disposition of drugs and their metabolites have been extensively described in the literature, based primarily on the analysis of plasma and urine. However, there are more limited data on their disposition in whole blood, which is often the only specimen available in forensic investigations and cases of driving under the influence of drugs. In this study, we have, for the first time, established pharmacokinetic properties of cocaine (COC) and its metabolites from concurrently collected whole blood and plasma samples, following a single 100 mg dose of cocaine hydrochloride administered via nasal insufflation to seven healthy volunteers. The median C of COC and its major metabolites, benzoylecgonine (BZE) and ecgonine methyl ester (EME), were closely related in whole blood and plasma. The median C for COC in plasma was 379.7 ng/mL (347.5-517.7) and 344.24 ng/mL (271.6-583.2) in whole blood. The median C for BZE in plasma was 441.2 ng/mL (393.6-475. and 371.18 ng/mL (371.1-477.3) in whole blood, EME was 105.5 ng/mL (93.6-151.8) in plasma and 135.5 ng/mL (87.8-183) in whole blood. Calculated medians of the whole blood to plasma ratio of COC (0.76), BZE (0.98) and EME (1.02) of approximately 1, strongly suggesting that the erythrocyte cell wall presents no barrier to COC and its metabolites. Furthermore, whole blood and plasma concentrations of COC were strongly correlated (R  = 0.0914 R = 0.956, p < 0.0001), as was BZE (R  = 0.0932 R = 0.965, p < 0.0001) and EME (R  = 0.0964R = 0.928, p < 0.0001). The minor oxidative metabolite norcocaine (NCOC) was detected in both whole blood and plasma at concentrations between 1 and 5 ng/mL within 60-180 minutes, suggesting that NCOC could be indicator of recent COC administration. Data from this study have shown for the first time that COC and its metabolites BZE and EME are evenly distributed between plasma and whole blood following controlled single-dose intranasal COC administration.
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http://dx.doi.org/10.1002/dta.2657DOI Listing
September 2019

Cold water extraction of codeine/paracetamol combination products: a case series and literature review.

Clin Toxicol (Phila) 2020 02 13;58(2):107-111. Epub 2019 May 13.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Tampering with opioid containing medications for use other than their prescribed indication is well documented; however, the published literature has concentrated on stronger, prescription opioids. Less potent opioids, such as codeine, are available without prescription in many European countries in the form of combination analgesic products and these can also be altered, with reports in particular of "cold-water extraction" being a tampering method achievable using household kitchen equipment. We searched a database of patients attending two South London emergency departments for cases of self-reported ingestion of the products of cold-water extraction, with subsequent review of their case notes. We searched the scientific and grey literature to identify current knowledge of this technique. We identified seven presentations in six patients, none of whom developed paracetamol toxicity or had concentrations suggesting ingestion of a significant dose of paracetamol. A review of the scientific literature on the method also demonstrated that the technique reduces recovered paracetamol in experimental laboratory settings. Additionally, the established literature characterizes the use of codeine in a recreational setting and reports one fatality associated with the method. Review of grey literature user-forums further describes recreational codeine use in relation to the method and frequent adverse events including hospital admission for paracetamol toxicity. Whilst the method appears capable of providing a recreational dose of codeine with reduction in the recovered paracetamol, it cannot be considered safe. Pharmaceutical production methods have been successfully developed to prevent tampering through other means but none thus far have been directed at the cold water extraction technique. Clinicians should be aware of the potential toxicity from tampered nonprescription analgesics. There is also the need for public health education regarding the potential risks associated with these methods.
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http://dx.doi.org/10.1080/15563650.2019.1612069DOI Listing
February 2020

Quantification of cocaine and cocaine metabolites in dried blood spots from a controlled administration study using liquid chromatography-tandem mass spectrometry.

Drug Test Anal 2019 May 13;11(5):709-720. Epub 2018 Dec 13.

Faculty of Pharmaceutical Sciences, Department of Bioanalysis, Laboratory of Toxicology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Cocaine is a common illicit stimulant and is mainly metabolized by hydrolysis to benzoylecgonine (BE) and ecgonine methyl ester (EME), but also to minor metabolites like norcocaine, or hydroxy-BE. When ethanol is present, cocaethylene is formed. Dried blood spot (DBS) sampling is a minimally invasive microsampling technique with possible advantages for analyte stability and ease of storage, making it an attractive matrix in forensic and clinical settings. We developed a liquid chromatography-tandem mass spectrometry-based (LC-MS/MS) method for quantifying cocaine, BE, EME, norcocaine, hydroxy-BE, and cocaethylene in DBS. Six-mm punches were extracted with aqueous buffer followed by protein precipitation, evaporation and reconstitution in mobile phase. Separation was achieved on a Polar-RP column (Phenomenex) in a 6-minute gradient including baseline-separation of norcocaine and BE. For MS detection, a QTRAP 5500 (Sciex) was used in positive electrospray ionization (ESI) multiple reaction monitoring (MRM) mode. The method was validated for selectivity, sensitivity [lower limited of quantification (LLOQ) 1.0-5.0 ng/mL], imprecision (≤13.4%, ≤19.6% at LLOQ), accuracy (≤ ± 14.9%), matrix effects, extraction efficiency (≥20.9%), hematocrit effect, volume spotted, punch location, long-term and autosampler stability. Concentrations in DBS from a controlled cocaine administration study in healthy volunteers were compared to whole blood and plasma. Although concentrations correlated moderately to strongly (Spearman's ρ 0.603-0.958), agreement between paired samples was poor, with overestimation of DBS concentrations and wide confidence intervals in Bland-Altman analysis. A possible cause are differences in capillary and venous blood concentrations, with the underlying mechanism requiring further research before DBS analysis for cocaine and its metabolites can be considered equivalent to whole blood or plasma analysis.
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http://dx.doi.org/10.1002/dta.2537DOI Listing
May 2019

Change in the new psychoactive substances associated with Emergency Department acute toxicity presentations associated with the introduction of the UK 2016 Psychoactive Substances Act.

Clin Toxicol (Phila) 2019 01 1;57(1):36-41. Epub 2018 Aug 1.

a Department of Clinical Toxicology , Guy's and St. Thomas' NHS Foundation Trust , London , UK.

Objectives: In May 2016, the Psychoactive Substances Act (PSA) came into effect in UK making it an offence to produce or supply new psychoactive substances (NPS). The aim of this study was to determine whether this was associated with a change in Emergency Department (ED) presentations with acute NPS toxicity.

Method: ED presentations to our inner-city hospital in London, UK, with acute NPS toxicity in the 12 months before and after the PSA introduction [June 2015-May 2016 (2015/2016) and June 2016-May 2017 (2016/2017)] were obtained from our database. The following data were extracted: (i) demographics; (ii) NPS(s) self-reported [categorized as synthetic cannabinoids (SC), cathinones, and "other NPS")]; and (iii) month of presentation.

Results: There were 1884 presentations with recreational drug toxicity, 447 (23.7%) involved NPS. There was no difference in the overall proportion of presentations involving an NPS in 2015/2016 [n = 196 (22.3%)] and 2016/2017 [251 (24.9%); (p = .48)]. There were a mean ± SD of 16.3 ± 3.7 NPS-related presentations per month in 2015/2016 and 20.9 ± 9.2 in 2016/2017; there was no significant change in overall monthly NPS-related presentations between these periods (p = .15). However, mean ± SD monthly SC-related presentations increased from 2015/2016 (5.9 ± 2.5) to 2016/2017 (17 ± 9.8); p = .004. Mean monthly cathinone-related presentations decreased from 2015/2016 (8.8 ± 4.2) to 2016/2017 (3.8 ± 2.7); p = .001. There was no significant change in monthly mean "other NPS" presentations from 2015/2016 (1.8 ± 2.2) to 2016/2017 (0.5 ± 0.8); p = .062. Between 2015/2016 and 2016/2017, SCs as a proportion of NPS-related presentations increased (r = .90) whilst cathinones decreased (r = -0.82).

Conclusion: NPS present front-line health services with unique challenges, and the PSA 2016 represents a major legislative effort in UK to limit their availability and supply. The burden of NPS use on this inner-city  ED remains large 12 months after this legislation has come into force, with evolving patterns of NPS use.
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http://dx.doi.org/10.1080/15563650.2018.1494277DOI Listing
January 2019

Gadolinium deposition and the potential for toxicological sequelae - A literature review of issues surrounding gadolinium-based contrast agents.

Br J Clin Pharmacol 2018 11 17;84(11):2522-2534. Epub 2018 Aug 17.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and Faculty of Life Sciences and Medicine, King's College London, London, UK.

Every year, approximately 30 million magnetic resonance imaging scans are enhanced with gadolinium-based contrast agents (GBCAs) worldwide. Although the development of nephrogenic systemic fibrosis in patients with renal impairment is well-documented, over recent years it has become apparent that exposure to GBCAs can potentially result in gadolinium deposition within human bone and brain tissue even in the presence of normal renal function. This review will address some of the controversies surrounding the safety of GBCA administration based on evidence from in vivo experiments, animal studies and clinical studies. We additionally evaluate the potential risk of toxicity from exposure to gadolinium in light of new guidance published by the US Food and Drug Administration and the European Medicines Agency, and discuss whether gadolinium deposition disease exists as a new diagnosis.
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http://dx.doi.org/10.1111/bcp.13718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177715PMC
November 2018

Assessment of the Availability, Cost, and Motivations for Use over Time of the New Psychoactive Substances-Benzodiazepines Diclazepam, Flubromazepam, and Pyrazolam-in the UK.

J Med Toxicol 2018 06 18;14(2):134-143. Epub 2018 Apr 18.

Clinical Toxicology Department, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Introduction: There has been increasing interest in the availability of non-prescription benzodiazepines and their sale as new psychoactive substances. We wanted to determine UK availability from Internet suppliers and motivations for use of three benzodiazepines (diclazepam, flubromazepam, and pyrazolam).

Methods: In November 2014 and March 2016, using the European Monitoring Centre for Drugs and Drug Addiction Snapshot Methodology, Internet search engines ( google.co.uk , uk. yahoo.com and ask.com.uk ) were searched using the terms 'buy diclazepam', 'buy flubromazepam' and 'buy pyrazolam'. Threads from drug-user forums ( bluelight.org , drugs-forum.com , erowid.org , legalhighsforum.com ) were analysed using a general inductive approach. Data were converted into price per gram/pellet to allow cost comparisons and to determine motivations for use.

Results: There was an increase in websites selling these benzodiazepines between 2014 and 2016: diclazepam (49 in 2014 to 55 in 2016), pyrazolam (33 to 35), and flubromazepam (39 to 45). Thirty-eight (63.3%) sites were based in the UK/Europe. Drugs were sold as pellets (49 websites, 81.7%), powder (19, 31.7%), and blotters (1, 1.7%). Pill forms were not available, and one (1.7%) website sold diclazepam/flubromazepam in liquid form. The cost reduced with increasing purchase quantities. Main motivations for use included anxiolysis, management of benzodiazepine withdrawal, sedation/sleep aid, and management of stimulant withdrawal.

Conclusions: These three benzodiazepines are widely available online, most commonly as pellets, and are (mis)used for a number of reasons. This study could be used to support triangulation of data from other sources to inform harm minimisation strategies.
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http://dx.doi.org/10.1007/s13181-018-0659-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962469PMC
June 2018

Metal-on-Metal Hip Joint Prostheses: a Retrospective Case Series Investigating the Association of Systemic Toxicity with Serum Cobalt and Chromium Concentrations.

J Med Toxicol 2017 12 12;13(4):321-328. Epub 2017 Sep 12.

School of Medicine, University of Colorado, Aurora, CO, USA.

Introduction: There have been concerns about prosthesis failure and the potential for systemic toxicity due to release of cobalt and chromium from metal-on-metal hip joint prostheses (MoM-HP). There is conflicting evidence on whether there is a correlation between higher cobalt and chromium concentrations and systemic toxicity.

Methods: We undertook a retrospective review of consecutive patients with MoM-HP referred for outpatient review in toxicology clinics in London, UK, and in the USA recorded in the Toxicology Investigators Consortium (ToxIC) Registry from June 2011 to June 2015.

Results: Thirty-one cases were identified; the median (IQR) serum cobalt concentration was 10.0 (3.8-32.8) mcg/L, and the median (IQR) serum chromium concentration was 6.9 (3.7-18.7) mcg/L. Twenty-three (74.2%) had symptoms, most commonly lethargy, hearing loss, and tinnitus. The odds ratios of symptomatic/asymptomatic patients for metal ion concentrations above/below 7 mcg/L were 1.87 (95% CI 0.37-9.57, p = 0.45) and 0.60 (95% CI 0.10-3.50, p = 0.57) for cobalt and chromium, respectively. Two (6.5%) patients with systemic cobalt toxicity had median (IQR) serum cobalt concentrations significantly higher than those without systemic features (630.4 [397.6-863.2] mcg/L versus 9.8 [2.9-16.4] mcg/L; p = 0.017). However, overall, there were no differences between cobalt (p = 0.38) or chromium (p = 0.92) concentrations between symptomatic and asymptomatic patients and no clinical features or investigation results correlated with cobalt or chromium concentration.

Conclusion: Two (6.5%) of 31 individuals referred for assessment of MoM-HP were diagnosed with systemic cobalt toxicity. However, despite a high prevalence of reported symptoms, neither symptoms nor investigation results correlated with serum cobalt or chromium concentrations.
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http://dx.doi.org/10.1007/s13181-017-0629-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711759PMC
December 2017

Analytical confirmation of synthetic cannabinoids in a cohort of 179 presentations with acute recreational drug toxicity to an Emergency Department in London, UK in the first half of 2015.

Clin Toxicol (Phila) 2017 Jun 20;55(5):338-345. Epub 2017 Feb 20.

a Clinical Toxicology , Guy's and St Thomas' NHS Foundation Trust , London , UK.

Context: Synthetic cannabinoid receptor agonists are the largest group of new psychoactive substances reported in the last decade; in this study we investigated how commonly these drugs are found in patients presenting to the Emergency Department with acute recreational drug toxicity.

Methods: We conducted an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with acute recreational drug toxicity. Residual serum obtained from a serum sample taken as part of routine clinical care was analyzed using high-resolution accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum clinical data were obtained from ED medical records.

Results: 18 (10%) of the 179 patient samples were positive for synthetic cannabinoid receptor agonists. The most common was 5F AKB-48 (13 samples, concentration 50-7600 pg/ml), followed by 5F PB-22 (7, 30-400 pg/mL), MDMB-CHMICA (7, 80-8000 pg/mL), AB-CHMINACA (3, 50-1800 pg/mL), Cumyl 5F-PINACA (1, 800 pg/mL) and BB-22 (1, 60 pg/mL). Only 9/18 (50%) in whom synthetic cannabinoid receptor agonists were detected self-reported synthetic cannabinoid receptor agonist use. The most common clinical features were seizures and agitation, both recorded in four (22%) individuals. Fourteen patients (78%) were discharged from the ED, one of the four admitted to hospital was admitted to critical care.

Conclusions: Synthetic cannabinoid receptor agonists were found in 10% of this cohort with acute recreational drug toxicity but self-reported in only half of these. This suggests that presentations to the ED with acute synthetic cannabinoid receptor agonist toxicity may be more common than reported.
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http://dx.doi.org/10.1080/15563650.2017.1287373DOI Listing
June 2017

Outcomes from massive paracetamol overdose: a retrospective observational study.

Br J Clin Pharmacol 2017 06 25;83(6):1263-1272. Epub 2017 Jan 25.

Austin Toxicology Service and Victorian Poisons Information Centre, Austin Hospital, Victoria, Australia.

Linked Article: This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163-5. https://doi.org/10.1111/bcp.13279 AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAP ) and treatment nomogram thresholds at those time points (APAP ) provides a useful assessment tool.

Methods: This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAP :APAP ratio (based on a treatment line through 100 mg l at 4 h), and time to acetylcysteine.

Results: Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P < 0.0001) and creatinine (r = 0.138, P = 0.002) concentrations. Acute liver injury, hepatotoxicity and coagulopathy were more frequent with APAP :APAP  ≥ 3 with odds ratios (OR) and 95% confidence intervals (CI) of 9.19 (5.04-16.68), 35.95 (8.80-158.1) and 8.34 (4.43-15.84), respectively (P < 0.0001). Heightened risk persisted in patients receiving acetylcysteine within 8 h of overdose.

Conclusion: Patients presenting following massive paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAP :APAP  ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort.
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http://dx.doi.org/10.1111/bcp.13214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427245PMC
June 2017

MDMB-CHMICA: Availability, Patterns of Use, and Toxicity Associated With This Novel Psychoactive Substance.

Subst Use Misuse 2017 01 19;52(2):223-232. Epub 2016 Oct 19.

b Department of Clinical Toxicology , St. Thomas Hospital , London , UK.

Background: MDMB-CHMICA (methyl 2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate) is a synthetic cannabinoid receptor agonist that has been detected in several recreational drug products in Europe since August 2014.

Objectives: This article aims to describe the prevalence of use, availability, and desired and adverse effects of MDMB-CHMICA.

Methods: Data were collated from published scientific literature, and systematic searches were conducted of publically available Internet sources (the "gray literature"), including websites offering to sell MDMB-CHMICA and Internet discussion forums featuring user reports.

Results: There are two case reports of fatalities in the published literature and one series of analytically confirmed cases of intoxication with MDMB-CHMICA. Seventy-eight websites offered to sell MDMB-CHMICA and a range of quantities were available with discounts for purchase of larger quantities (from 0.25 g at $27.95/g to 100 kg at $1.28/g). We identified 36 reports from MDMB-CHMICA users on Internet discussion forums dated October 2014 onwards. The most common positive effect reported by users was euphoria (11; 30.6%) and almost all reports (33; 91.7%) described one or more adverse effects, most commonly palpitations (11; 30.6%), vomiting (9; 25.0%), loss of consciousness (6; 16.7%), visual hallucinations (6; 16.7%), chest pain (5; 13.9%), and anxiety (5; 13.9%).

Conclusions: This systematic review of qualitative and scientific data relating to MDMB-CHMICA shows that it is widely available from Internet-based suppliers. Users describe a spectrum of effects that are consistent with other synthetic cannabinoids, but there was a high prevalence of adverse effects, and both users and suppliers warn of its high potency.
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http://dx.doi.org/10.1080/10826084.2016.1223692DOI Listing
January 2017

Management of body stuffers presenting to the emergency department.

Eur J Emerg Med 2016 Dec;23(6):425-429

aClinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners bKing's College London, London, UK cPoison Control Center Bergamo, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Objective: The aim of this study was to establish a management protocol for body stuffers presenting to the emergency department.

Methods: This is a retrospective observational case series of patients presenting to the emergency department of a large inner-city hospital as 'body stuffers' during the period between 1 January 2006 and 31 October 2011, irrespective of the type of drug ingested. We reviewed demographic data, ingestion characteristics, clinical progress and outcome.

Results: A total of 126 patients were included in the study, with a mean age of 31±8.10 years (range 15-58 years), among whom 106 were male (84%). Drugs ingested were as follows: heroin (n=61, 48%), cocaine (n=58, 46%), other drugs (n=20, 16%) and unknown (n=10, 8%). Of the patients, 23 (18%) ingested more than one drug. At presentation, 96 had features of drug toxicity. The presence of depressant drug toxidrome was more commonly observed among heroin users, but stimulant drug toxidromes were seen across all groups. Of the patients, 12 developed changes in clinical state, with a mean time to development of symptoms of 2 h 50 min±1 h 39 min (range from 1 h 0 min to 5 h 36 min). Abdominal radiography showed the presence of foreign bodies in 8% of the tests performed, and packets were recovered from one patient who underwent gut decontamination.

Conclusion: Patients developed new or worsening features of drug toxicity within 6 h of presentation. Toxidromes observed are often not drug/class specific, and treatment including gut decontamination and radiography do not aid in expediting discharge. We propose an observation period of 6 h from the time of admission as the time required if the patient is asymptomatic or there is resolution of presenting signs and symptoms.
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http://dx.doi.org/10.1097/MEJ.0000000000000277DOI Listing
December 2016

Prevalence of Use of Electronic Nicotine Delivery Systems (ENDS) to Vape Recreational Drugs by Club Patrons in South London.

J Med Toxicol 2017 03 6;13(1):61-65. Epub 2016 Sep 6.

Clinical Toxicology, Guys and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Introduction: Electronic nicotine delivery systems (ENDS, often called e-cigarettes) are nicotine delivery devices that heat nicotine into vapour that is inhaled, a process called 'vaping'. Use eclipsed nicotine-replacement therapy (NRT) in 2014 but ENDS role in smoking cessation remains controversial. Safety has not been proven and there have been reports to US poison centres regarding potential ENDS-related nicotine toxicity. A further concern is use of ENDS to vape recreational drugs, but there is limited data to substantiate this. The aim of this study was to report on ENDS use to vape recreational drugs in patrons of a South London nightclub where high prevalence of recreational drug use has previously been shown.

Methods: A convenience sample of 101 participants was surveyed in March 2015 as part of a larger survey on drug use. Individuals were asked if they used ENDS to vape nicotine and/or other substances (and if so which substances).

Results: Ninety (89.1 %) of respondents were male with median age of 28 years (IQR 23-34). Eighty (79.2 %) currently smoked cigarettes; 20 (19.8 %) currently used ENDS for nicotine. Six (5.9 %) reported using ENDS to take other substances: 2 for 'liquid cannabis' and 4 did not elaborate on the substance(s) used. Of these 6, 3 were using ENDS to vape nicotine and 3 had never used them for nicotine.

Conclusion: 5.9 % of individuals in this sample reported using ENDS to vape substances other than nicotine. Further work is required in larger populations to determine how common this is, evaluate which agents are being vaped and to inform appropriate public education.
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http://dx.doi.org/10.1007/s13181-016-0583-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330959PMC
March 2017

Microwave-assisted on-spot derivatization for gas chromatography-mass spectrometry based determination of polar low molecular weight compounds in dried blood spots.

J Chromatogr A 2016 Sep 26;1465:175-83. Epub 2016 Aug 26.

Laboratory of Toxicology, Ghent University, Ghent, Belgium. Electronic address:

Dried blood spot (DBS) sampling and analysis is increasingly being applied in bioanalysis. Although the use of DBS has many advantages, it is also associated with some challenges. E.g. given the limited amount of available material, highly sensitive detection techniques are often required to attain sufficient sensitivity. In gas chromatography coupled to mass spectrometry (GC-MS), derivatization can be helpful to achieve adequate sensitivity. Because this additional sample preparation step is considered as time-consuming, we introduce a new derivatization procedure, i.e. "microwave-assisted on-spot derivatization", to minimize sample preparation of DBS. In this approach the derivatization reagents are directly applied onto the DBS and derivatization takes place in a microwave instead of via conventional heating. In this manuscript we evaluated the applicability of this new concept of derivatization for the determination of two polar low molecular weight molecules, gamma-hydroxybutyric acid (GHB) and gabapentin, in DBS using a standard GC-MS configuration. The method was successfully validated for both compounds, with imprecision and bias values within acceptance criteria (<20% at LLOQ, <15% at 3 other QC levels). Calibration lines were linear over the 10-100μg/mL and 1-30μg/mL range for GHB and gabapentin, respectively. Stability studies revealed no significant decrease of gabapentin and GHB in DBS upon storage at room temperature for at least 84 days. Furthermore, DBS-specific parameters, including hematocrit and volume spotted, were evaluated. As demonstrated by the analysis of GHB and gabapentin positive samples, "microwave-assisted on-spot derivatization" proved to be reliable, fast and applicable in routine toxicology. Moreover, other polar low molecular weight compounds of interest in clinical and/or forensic toxicology, including vigabatrin, beta-hydroxybutyric acid, propylene glycol, diethylene glycol, 1,4-butanediol and 1,2-butanediol, can also be detected using this method.
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http://dx.doi.org/10.1016/j.chroma.2016.08.057DOI Listing
September 2016

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

Br J Clin Pharmacol 2017 02 29;83(2):393-399. Epub 2016 Sep 29.

Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Background: Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance.

Methods: A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion.

Results: Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml (-6.7 to -2.3) for the first infusion, +0.2 mg ml (-0.9 to +0.4) for the second infusion and -0.3 mg ml (-0.6 to +0.2) for third and fourth infusions.

Conclusion: There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors.
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http://dx.doi.org/10.1111/bcp.13099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237694PMC
February 2017

Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation.

J Med Toxicol 2016 12 25;12(4):396-401. Epub 2016 Jul 25.

Department of Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Introduction: Synthetic Cannabinoid Receptor Agonists (SCRAs) are the largest group of new psychoactive substances reported to the European Warning System and the United Nations Office on Drugs and Crime to date. The heterogeneous nature and speed of diversification of these compounds make it challenging to accurately characterise and predict harms of these compounds in pre-clinical studies, ahead of their appearance.

Case Report: We report the case of a 19-year-old female who purchased three products from a headshop: two new psychoactive substances (sachets of "cannabis tea" and "mushroom tea") as well as two LSD blotters. After the "cannabis tea" was smoked and the two LSD blotters and "mushroom tea" were ingested, the patient became tachycardic (HR 128), developed seizures, agitation, visual hallucinations as well as suspected serotonergic toxicity (sustained ankle clonus 20-30 beats) 1-2 hours after use. She was treated with 1 mg of intravenous midazolam. Symptoms/signs resolved within 13 hours. No further supportive care was required. Plasma, blood, and urine samples confirmed the presence of two SCRAs: 5FAKB-48 and 5F-PB-22. The patient also reported therapeutic use of both fluoxetine and citalopram for depression.

Discussion: To the best of our knowledge, this is the first case report of non-fatal intoxication with 5F-AKB-48 with analytical confirmation and exposure times. It also highlights the difficulties in understanding the pattern of toxicity of certain SCRAs in the context of psychotropic medications/co-morbid mental illness.
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http://dx.doi.org/10.1007/s13181-016-0571-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135680PMC
December 2016

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose.

Br J Clin Pharmacol 2016 11 10;82(5):1358-1363. Epub 2016 Aug 10.

Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Background: The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen.

Method: A 6-month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays.

Results: From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50-163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217-413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95-260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems.

Conclusion: Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge.
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http://dx.doi.org/10.1111/bcp.13063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061798PMC
November 2016

Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity.

Drug Alcohol Rev 2016 09 23;35(5):591-6. Epub 2015 Dec 23.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Introduction And Aims: There has been a global increase in the availability and use of novel psychoactive substances (NPS) over the last decade. Phenibut (β-phenyl-γ-aminobutyric acid) is a GABAB agonist that is used as an NPS. Here, we bring together published scientific and grey information sources to further understand the prevalence of use, desired effects and acute toxicity of phenibut.

Design And Methods: Using European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, we undertook an English language Internet snapshot survey in May 2015 to gather information on the availability and price of phenibut from Internet NPS retailers. To gather information on prevalence of use, desired effects and/or adverse effects, we searched grey literature (online drug discussion forums) and medical literature (PubMed and abstracts from selected International Toxicology conferences).

Results: We found 48 unrelated Internet suppliers selling phenibut in amounts ranging from 5 g (US$1.60, £1.01/g) to 1000 kg (US$0.23, £0.14/g). Capsules containing 200-500 mg of phenibut were available in packs of between 6 (US$4.45, £2.80/g) and 360 (US$0.43, £0.27/g). According to the grey literature, phenibut is taken for its anxiolytic and euphoric properties, with tolerance and withdrawal syndromes commonly reported adverse effects. Phenibut is taken orally at an average dose of 2.4 g. Case reports in the medical literature feature users who present to emergency departments heavily sedated or experiencing withdrawal. There have been no reported deaths relating to phenibut use.

Discussion And Conclusions: Phenibut is readily available in the UK from Internet sites selling NPS. Its desired and adverse effects appear similar to other gamma-aminobutyric acid receptor agonists. [Owen DR, Wood DM, Archer JRH, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity. Drug Alcohol Rev 2016;35:591-596].
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http://dx.doi.org/10.1111/dar.12356DOI Listing
September 2016

Availability of prescription zopiclone over the internet.

BMJ 2015 Nov 4;351:h5710. Epub 2015 Nov 4.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK

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http://dx.doi.org/10.1136/bmj.h5710DOI Listing
November 2015

Ethylphenidate: availability, patterns of use, and acute effects of this novel psychoactive substance.

Eur J Clin Pharmacol 2015 Oct 22;71(10):1185-96. Epub 2015 Jul 22.

Clinical Toxicology, St. Thomas̕ Hospital, 3rd Floor, Block C, South Wing, Westminster Bridge Road, London, SE1 7EH, UK.

Purpose: Ethylphenidate is a novel psychoactive substance that is an analogue of methylphenidate. This paper describes its availability, patterns of use, and acute effects.

Methods: Searches of the scientific and grey literature (publicly accessible Internet resources) were undertaken, using the keywords "Ethylphenidate", "Ethyl phenidate", "Ethyl phenyl(piperidin-2-yl)acetate", and "Nopaine", to identify information on the prevalence and patterns of use, desired effects, and toxicity of ethylphenidate. An Internet snapshot survey was performed on 10 February 2015 to provide information on availability and cost of ethylphenidate.

Results: The literature search identified 1 case series of acute recreational ethylphenidate toxicity, 1 case report of ethylphenidate dependence, 1 qualitative analysis of user reports on Internet drug forums, 2 conference abstracts for surveillance studies, 1 report of two cases of ethylphenidate detected in post-mortem analyses, and 198 user reports on Internet discussion forums and social media sites. The Internet snapshot survey found 83 websites selling ethylphenidate, with purchase prices ranging from £28.20 ± 0.63 (€37.71 ± 0.85) per gram for a 500-mg amount to £2.64 ± 0.57 (€3.53 ± 0.77) per gram for 1 kg. The published cases and Internet user reports suggest the acute effects of ethylphenidate are similar to other stimulant drugs; the most common route of use was by nasal insufflation. The most common desired effects were euphoria, stimulation, and increased concentration, sociability, and energy levels; the most common unwanted effects included anxiety, palpitations, insomnia, and paranoia.

Conclusion: This review of the scientific and grey literature has demonstrated that the acute harms associated with its use are stimulant in nature and that ethylphenidate is widely available to users over the Internet, with significant discounts for bulk purchases.
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http://dx.doi.org/10.1007/s00228-015-1906-zDOI Listing
October 2015

Safety of metformin in patients with chronic obstructive pulmonary disease and type 2 diabetes mellitus.

COPD 2015 Apr;12(2):126-31

1Clinical Pharmacology, Institute of Infection and Immunity, St George's, University of London , London , UK.

Type 2 diabetes mellitus (T2DM) is commonly associated with chronic obstructive pulmonary disease (COPD). Metformin is a valuable treatment for T2DM, and may offer additional benefits in COPD. However, due to its rare association with lactic acidosis, its safety in COPD is uncertain. We retrospectively identified patients with T2DM who had been admitted to hospital for COPD exacerbations. We compared those who were taking metformin with those who were not, with respect to their lactate concentration (primary endpoint) and survival (secondary endpoint). The study cohort (n = 130) had a mean (±standard deviation) age of 73.0 ± 9.8 years and 47 (36%) were female. Arterial blood gases were recorded in 120 cases: 88 (73%) were hypoxemic, 45 (38%) were in respiratory failure and 33 (28%) had respiratory acidosis. The 51 patients (39%) in the metformin group had a median (interquartile range) lactate concentration of 1.45 mmol/L (1.10-2.05) versus 1.10 mmol/L (0.80-1.50) in the non-metformin group (p = 0.012). Median survival was 5.2 years (95% CI 4.5-5.8) versus 1.9 years (1.1-2.6), respectively (hazard ratio 0.57; 95% CI 0.35-0.94). This remained significant in a multivariate model adjusted for measurable confounders. In conclusion, among patients with COPD at high risk for lactate accumulation, metformin therapy was associated with a minor elevation of lactate concentration of doubtful clinical significance. Metformin was associated with a survival benefit, but this must be interpreted cautiously due to possible effects from unmeasured confounders. Viewed collectively, the results suggest that COPD should not present a barrier to the investigational or clinical use of metformin.
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http://dx.doi.org/10.3109/15412555.2015.898052DOI Listing
April 2015

Running an unknown risk: a marathon death associated with the use of 1,3-dimethylamylamine (DMAA).

Drug Test Anal 2015 May 13;7(5):433-8. Epub 2015 Jan 13.

Drug Control Centre, Department of Forensic and Analytical Science, Analytical and Environmental Sciences Division, King's College London, London, UK.

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http://dx.doi.org/10.1002/dta.1764DOI Listing
May 2015

What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient?

Clin Toxicol (Phila) 2015 Mar 29;53(3):145-50. Epub 2015 Jan 29.

Guy's and St Thomas' NHS Foundation Trust and King's Health Partners , London , UK.

Context: Intravenous lipid emulsion (ILE) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are being used together or in close succession in the management of circulatory failure secondary to cardiotoxic drug poisoning. There have been reports of mechanical problems, including fat emulsion agglutination, clogging, increased blood clot formation and even cracking of parts of the machine, in patients concurrently receiving VA-ECMO and ILE as part of parenteral nutrition.

Objective: To ascertain the adverse effects associated with the combined use of ILE and ECMO in the poisoned patient.

Methods: PubMed and OVID (1966 to 9 June 2014) and EMBASE (1947 to 9 June 2014) were searched to identify publications relating to studies and/or case reports where ILE had been used at the same time when VA-ECMO was used - 7 were identified. In addition, the abstracts published between 2006 and 2013 inclusive of those from the North American Congress of Clinical Toxicology and the congresses of the European Association of Poisons Centres and Clinical Toxicologists were searched to identify additional cases and 2 were found. Finally all cases posted on lipidrescue.org were reviewed to determine if they related to the use of ILE with VA-ECMO and no new cases were identified. In vitro study. An in vitro study involving the continuous infusion of 20% ILE at 3 mL/h for 24 h demonstrated layering (separation of intact fat emulsion from blood) and agglutination (clumping resulting in little or no flow of fat emulsion through the circuit) in all circuits within 30 min of starting the fat emulsion infusion.

Clinical Studies: An observational study based in 42 centres that regularly used 'fat emulsion' during VA-ECMO treatment reported cracking of stopcocks (the valve which restricts flow in the VA-ECMO tubing) (n = 10, 23.8%); fat emulsion agglutination (n = 11, 26.2%); clogging and associated malfunction of the membrane oxygenator (n = 2, 4.8%); and increased blood clot formation in the circuits (n = 2, 4.8%). In a prospective observational study of 9 neonates on VA-ECMO receiving intravenous nutrition, layering and agglutination were seen in four sets of VA-ECMO tubing and blood clots were found in seven circuits. Nine case reports were identified where ILE was used with VA-ECMO for the management of circulatory failure/instability secondary to cardiotoxic drug poisoning. In two of these case reports, the authors specifically stated that ILE did not cause any mechanical complications with the VA-ECMO; the other seven reports made no comment as to whether there were any complications or not.

Conclusions: There is in vitro and clinical evidence that the combined use of ILE and extracorporeal membrane oxygenation may be associated with fat deposition in the VA-ECMO circuits and increased blood clot formation. Clinicians managing poisoned patients with both of these novel treatment modalities should be aware of these potential complications.
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http://dx.doi.org/10.3109/15563650.2015.1004582DOI Listing
March 2015

Do capillary dried blood spot concentrations of gamma-hydroxybutyric acid mirror those in venous blood? A comparative study.

Drug Test Anal 2015 Apr 6;7(4):336-40. Epub 2015 Jan 6.

Laboratory of Toxicology, Ghent University, Ghent, Belgium.

Gamma-hydroxybutyric acid (GHB) is a well-known illicit club and date-rape drug. Dried blood spot (DBS) sampling is a promising alternative for classical venous sampling in cases of (suspected) GHB intoxication since it allows rapid sampling, which is of interest for the extensively metabolized GHB. However, there is limited data if -and how- capillary DBS concentrations correlate with venous concentrations. We conducted a comparative study in 50 patients with suspected GHB intoxication, to determine and to correlate GHB concentrations in venous DBS (vDBS) and capillary DBS (cDBS). This is the first study that evaluates in a large cohort the correlation between capillary and venous concentrations of an illicit drug in real-life samples. Of the 50 paired samples, 7 were excluded: the vDBS concentration was below the LLOQ of 2 µg/mL in 3 cases and 4 samples were excluded after visual inspection of the DBS. Bland-Altman analysis revealed a mean % difference of -2.8% between cDBS and vDBS concentrations, with the zero value included in the 95% confidence interval of the mean difference in GHB concentration. A paired sample t-test confirmed this observation (p = 0.17). Also the requirement for incurred sample reproducibility was fulfilled: for more than two-thirds of the samples the concentrations obtained in cDBS and those in vDBS were within 20% of their mean. Since equivalent concentrations were observed in cDBS and vDBS, blood obtained by fingerprick can be considered a valid alternative for venous blood for GHB determination.
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http://dx.doi.org/10.1002/dta.1760DOI Listing
April 2015

Development of a 'patient information leaflet' for use following assessment of patients with reported or suspected paracetamol overdose in the UK.

Pharmacol Res Perspect 2014 Dec 1;2(6):e00075. Epub 2014 Sep 1.

Medicine, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners London, United Kingdom ; Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners London, United Kingdom ; King's College London London, United Kingdom.

The aim of this study was to design an information leaflet for patients with paracetamol overdose based on Medicines and Healthcare products Regulatory Agency guidance and to assess its readability. A two-sided one page information leaflet was designed for patients being discharged from hospital after a paracetamol overdose. Patients presenting with an acute paracetamol overdose, irrespective of whether they were treated or not, were recruited to read the leaflet and then answer a brief structured questionnaire based on the leaflet. The readability of the information leaflet was assessed using the Flesch reading ease score. Thirty patients (15 male, 12 female, 3 not recorded; mean age 38 ± 13.0 years) were recruited, wherein 100% of patients reported the language used was understandable, 96.6% knew which symptoms would require urgent medical review after discharge and 100% of patients knew the liver was affected by paracetamol. The Flesch reading ease score was 67.6 (out of a maximum of 100), equivalent to a UK reading age of 10-11years old. Our information leaflet for all patients being discharged after paracetamol overdose was well received by patients, provided them with the required knowledge and had an appropriate reading age based on UK literacy rates. We would recommend that this leaflet could be used as a template on a national level, localized to individual hospitals, to improve patient knowledge of paracetamol toxicity, and facilitate early medical review in the event of deterioration following discharge from the hospital.
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http://dx.doi.org/10.1002/prp2.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186451PMC
December 2014

Safety of Metformin in Patients with Chronic Obstructive Pulmonary Disease and Type 2 Diabetes Mellitus.

COPD 2015 Apr 10;12(2):126-131. Epub 2014 Jun 10.

a 1 Clinical Pharmacology, Institute of Infection and Immunity, St George's, University of London , London , UK.

Type 2 diabetes mellitus (T2DM) is commonly associated with chronic obstructive pulmonary disease (COPD). Metformin is a valuable treatment for T2DM, and may offer additional benefits in COPD. However, due to its rare association with lactic acidosis, its safety in COPD is uncertain. We retrospectively identified patients with T2DM who had been admitted to hospital for COPD exacerbations. We compared those who were taking metformin with those who were not, with respect to their lactate concentration (primary endpoint) and survival (secondary endpoint). The study cohort (n = 130) had a mean (±standard deviation) age of 73.0 ± 9.8 years and 47 (36%) were female. Arterial blood gases were recorded in 120 cases: 88 (73%) were hypoxemic, 45 (38%) were in respiratory failure and 33 (28%) had respiratory acidosis. The 51 patients (39%) in the metformin group had a median (interquartile range) lactate concentration of 1.45 mmol/L (1.10-2.05) versus 1.10 mmol/L (0.80-1.50) in the non-metformin group (p = 0.012). Median survival was 5.2 years (95% CI 4.5-5.8) versus 1.9 years (1.1-2.6), respectively (hazard ratio 0.57; 95% CI 0.35-0.94). This remained significant in a multivariate model adjusted for measurable confounders. In conclusion, among patients with COPD at high risk for lactate accumulation, metformin therapy was associated with a minor elevation of lactate concentration of doubtful clinical significance. Metformin was associated with a survival benefit, but this must be interpreted cautiously due to possible effects from unmeasured confounders. Viewed collectively, the results suggest that COPD should not present a barrier to the investigational or clinical use of metformin.
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http://dx.doi.org/10.3109/15412555.2014.898052DOI Listing
April 2015

Acute toxicity associated with analytically confirmed recreational use of methiopropamine (1-(thiophen-2-yl)-2-methylaminopropane).

J Med Toxicol 2014 Sep;10(3):299-302

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK,

Purpose: Methiopropamine use in Europe has been detected since January 2011, but there is limited information on its acute toxicity. Here, we describe a case of analytically confirmed methiopropamine acute toxicity.

Case Report: A 27-year-old woman with no previous medical history was brought to the emergency department with palpitations, chest tightness, anxiety, nausea, vomiting and visual hallucinations following the use of a 'Quicksilver'. Toxicological analysis of her urine collected at presentation to the ED detected methiopropamine at a concentration of 400 ng/mL. Other drugs were also detected but at a much lower concentration.

Conclusion: This is the first ever case report of analytically confirmed acute toxicity related to methiopropamine use. It confirms the potential for significant acute toxicity with cardiovascular, gastrointestinal and psychotic symptoms thus providing further information to help with managing these patients and allow legislative authorities to consider the need for its control.
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http://dx.doi.org/10.1007/s13181-014-0399-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141929PMC
September 2014

How to use toxicology screening tests.

Arch Dis Child Educ Pract Ed 2012 Oct 21;97(5):194-9. Epub 2012 Jul 21.

Department of Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1136/archdischild-2012-301792DOI Listing
October 2012
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