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.

Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.

INTRODUCTION: Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. CASE REPORT: A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 µg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. DISCUSSION: Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.

Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone.

BACKGROUND: There is evidence of increasing use of the synthetic cathinone mephedrone (4-methylmethcathinone), particularly amongst clubbers. However, there have only two single case reports of mephedrone toxicity. The aim of this study is to report the pattern of clinical toxicity seen with mephedrone use. CASE SERIES: We describe 15 patients who presented to our Emergency Department following self-reported mephedrone use. Significant clinical features seen included agitation in 53.3%, tachycardia in 40%, systolic hypertension in 20% and seizures in 20%. Twenty per cent required treatment with benzodiazepines, predominantly for management of agitation. All patients were discharged with no sequelae. Previous user reports have suggested that mephedrone use is associated with cool/blue peripheries; this was not seen in any of the patients in our series. CONCLUSION: The pattern of toxicity seen with mephedrone in this series is similar to that seen with 1-benzylpiperazine which has recently been classified under UK and EU misuse of drugs legislation. On the basis of this, together with a recent confirmed mephedrone related death in Sweden, we feel that appropriate assessments should be undertaken to determine the legal status of mephedrone.

Improvement in the management of acutely poisoned patients using an electronic database, prospective audit and targeted educational intervention.

PROBLEM: The need to improve the clinical assessment and management of acutely poisoned patients presenting to an NHS hospital emergency department (ED). DESIGN: Creation of an electronic clinical toxicology database to prospectively collect all aspects of clinical information on poisoned-patient presentations. Systematic analysis of collated information to identify shortfalls in patient assessment and management. Bimonthly audit meetings, and design and implementation of educational interventions to address identified shortfalls. Ongoing audit to demonstrate continued improvement in patient care. BACKGROUND AND SETTING: ED in tertiary-level inner-city London teaching hospital. Study conducted by staff from the ED and clinical toxicology service. KEY MEASURES FOR IMPROVEMENT: Demonstration of overall reduction in the incidence of predefined shortfalls in patient assessment and management during 12-month study period. STRATEGIES FOR IMPROVEMENT: Targeted educational lectures and case-based clinical scenarios addressing identified deficiencies in the knowledge required to effectively manage poisoned patients. Weekly case-based anonymised feedback report sent electronically to staff involved in caring for poisoned patients. EFFECTS OF CHANGE: Implementation of targeted teaching of ED staff and regular electronic distribution of teaching cases. Between the first and second 6 months of the study, there was a significant increase in the proportion of presentations for which clinical management was graded as "good" (77.6% to 89.4%, p<0.0001) and a significant reduction in the proportion of "major" (9.9% to 5.8%, p = 0.012) and "minor" (12.6% to 4.8%, p<0.0001) shortfalls. LESSONS LEARNT: Systematic collection of clinical information, using a dedicated electronic database and subsequent review and audit of collated data by interested clinicians, enabled design and implementation of targeted educational interventions to address shortfalls in patient management. This process has led to significant improvements in the clinical care of acutely poisoned patients presenting to the ED.

Doctors' knowledge of the appropriate use and route of administration of antidotes in the management of recreational drug toxicity.

BACKGROUND: Specific antidotes (eg, naloxone, flumazenil, cyproheptadine and benzodiazepines) are available for the management of certain recreational drug-induced toxicities. Some controversies surround the use of some of these antidotes, especially flumazenil in benzodiazepine toxicity. There are no previously published data on doctors' knowledge of the use of these specific antidotes. METHODS: A questionnaire survey was designed to determine internal/emergency medicine doctors' knowledge of the appropriate use of antidotes in the management of clinical scenarios of acutely poisoned patients. For nine simulated clinical scenarios of acute toxicity from recreational drugs (benzodiazepines, cocaine, N-methyl-L-(3,4-methylene-dioxyphenyl)-2-aminopropane (MDMA)-induced serotonin toxicity and opioids), they were asked to indicate whether the suggested antidote and route of administration were correct. RESULTS: 42 physicians of all grades completed the questionnaire. The mean correct score was 5.4 (SD 1.1) (median 6, interquartile range 5-7). The percentages correct for the various clinical scenarios were 68.3% for opioid toxicity, 81% for benzodiazepine toxicity, 28.6% for MDMA-induced serotonin toxicity and 70.2% for cocaine toxicity. Doctors were more likely to record an answer of "unsure" for the use of cyproheptadine in ST serotonin toxicity (28.6%) compared with the use of the other antidotes (1.4%; p<0.001). CONCLUSION: Knowledge of the appropriate use of antidotes in recreational drug toxicity is not consistent, with poorer knowledge on the use of newer antidotes such as cyproheptadine in serotonin toxicity. Education is required both to increase overall knowledge on the use of specific antidotes in the management of recreational drug-induced toxicity, as well as focusing on newer antidotes such as cyproheptadine.

Medical and legal confusion surrounding gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD).

BACKGROUND: Gamma-hydroxybutyrate (GHB) is used as a recreational drug, with significant associated morbidity and mortality; it is therefore a class C drug under the Misuse of Drugs Act (1971). However, its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD) remain legally available despite having similar clinical effects. AIM: The aim of this study was to determine whether the relative proportions of self-reported ingestions of GHB or its precursors GBL and 1,4BD were similar to those seen in analysis of seized drugs. DESIGN AND METHODS: Retrospective review of our clinical toxicology database to identify all cases of self-reported recreational GHB, GBL and 1,4BD use associated with ED presentation in 2006. Additionally all seized substances on people attending local club venues were analysed by a Home Office approved laboratory to identify any illicit substances present. RESULTS: In 2006, there were a total of 158 ED presentations, of which 150 (94.9%) and 8 (5.1%) were GHB and GBL self-reported ingestions respectively; 96.8% (153) were recreational use. Of the 418 samples seized, 225 (53.8%) were in liquid form; 85 (37.8%) contained GHB and 140 (62.2%) contained GBL. None of the seized samples contained 1,4BD and there were no self-reported 1,4BD ingestions. CONCLUSION: Self-reported GHB ingestion was much more common than GBL ingestion, whereas GBL was more commonly found in the seized samples. These differences suggest that GBL use may be more common than previously thought and we suggest that there should be further debate about the legal status of the precursors of GHB.

What evidence is there that the UK should tackle the potential emerging threat of methamphetamine toxicity rather than established recreational drugs such as MDMA ('ecstasy')?

BACKGROUND: There is increasing interest in whether methamphetamine is an emerging recreational drug in the UK. AIM: To determine what evidence is there that methamphetamine use is an emerging drug in the UK compared to established recreational drugs such as MDMA. DESIGN AND METHODS: We undertook a retrospective study collating data on the number of enquiries to both our poisons centre and the UK National Poisons Information Service (NPIS) relating to all recreational drugs, methamphetamine and MDMA; presentations to our Emergency Department (ED) with acute methamphetamine toxicity and the frequency of positive urine tests for methamphetamine and MDMA in workplace drug screening programmes. RESULTS: There was a small increase in the number of methamphetamine-related calls to our poisons centre, but it remained uncommon (0.1% of all recreational drugs cases in 2000 to 1.23% in 2006) compared to MDMA (17.3-42.7% of all recreational drugs cases). The number of 2005/6 enquiries to the UK NPIS for methamphetamine was 12, compared to 455 MDMA enquiries (0.014 and 0.52% of all enquiries, respectively). There were five presentations to our ED relating to methamphetamine over a 15-month period compared to 171 for MDMA. Of the 254 440 urine samples screened for the presence of drugs in the workplace (2000-06), three were positive for methamphetamine and 147 for MDMA. CONCLUSION: There is no evidence of increasing use of methamphetamine or that acute methamphetamine poisoning is a significant clinical problem compared to established recreational drugs such as MDMA. In our opinion, healthcare, educational and law enforcement resources should be proportionally directed towards tackling drugs that pose an immediate and continuing healthcare risk to the population rather than emerging recreational drugs.

What's being used to spike your drink? Alleged spiked drink cases in inner city London.

OBJECTIVES: To determine the incidence and character of drink spiking in an urban population of patients within the UK presenting to an emergency department concerned they had consumed a deliberately contaminated drink. STUDY DESIGN: Prospective case series determining the presence and quantity of sedative and illicit drugs, and ethanol in biological samples (blood and urine) obtained from consenting patients >18 years of age presenting to a large inner city London emergency department alleging they had consumed a spiked drink within the previous 12 h. RESULTS: Biological samples were obtained from 67 (blood) and 75 (urine) of 78 study participants. 82% of participants were female, mean age 24 years. Mean time from alleged exposure to biological sampling was 5.9 h (range 1-12 h). Ethanol was detected in 89.7% of participants. Mean serum ethanol concentration was 1.65 g/l (range 0.04-3.1 g/l); 60% of participants had a serum ethanol concentration associated with significant intoxication (>1.5 g/l). Illicit drugs were detected in 12 (15%) participants; 7 denied intentional exposure (3 methylenedioxymethamphetamine, 3 cannabis, 1 gamma-hydroxybutyrate). Medicinal drugs were detected in 13 participants; only 1 exposure was unexplained (benzodiazepine). Overall illicit or medicinal drugs of unexplained origin were detected in 8 (10%) participants. Unexplained sedative drug exposure was detected in only 2 (3%) participants. CONCLUSIONS: Use of sedative drugs to spike drinks may not be as common as reported in the mainstream media. A large number of study participants had serum ethanol concentrations associated with significant intoxication; the source (personal over-consumption or deliberate drink spiking) is unclear.

Paracetamol availability and recent changes in paracetamol poisoning: is the 1998 legislation limiting availability of paracetamol being followed?

OBJECTIVE: To determine the degree of adherence to legislation introduced in 1998 restricting the availability of over the counter paracetamol. DESIGN: A prospective observational study. SETTING: An emergency department in an inner city London teaching hospital. Pharmacy and non-pharmacy outlets in south London. MAIN OUTCOME MEASURES: (1) The source of paracetamol ingested by 107 patients presenting with an acute paracetamol overdose (2001-2003) and (2) the ability to purchase paracetamol from pharmacy and non-pharmacy outlets in a manner contravening paracetamol pack size legislation (2004). RESULTS: Potentially toxic amounts of paracetamol in excess of pack size restrictions were purchased in 70% (17 of 24) of outlets. Forty six per cent of patients who had ingested a potentially toxic dose of paracetamol obtained the tablets in a manner contravening the 1998 legislation. CONCLUSION: Legislation limiting the availability of over the counter paracetamol is not being adhered to in south London. A significant number of patients ingesting a potentially toxic dose of paracetamol report purchasing the tablets in a manner contravening the legislation. Studies that attempt to assess the impact of the legislation need to be interpreted in the context of these results. Measures to enforce current legislation may help to reduce the severity of paracetamol poisoning in the UK.

Prehospital activated charcoal: the way forward.

OBJECTIVES: Single dose activated charcoal (SDAC) may be an effective method of gastric decontamination when administered to patients within an hour of drug overdose. However, few patients who may benefit from this treatment attend an emergency department within this timeframe. The authors sought to determine the current attitudes of ambulance NHS trusts to recent recommendations that the administration of SDAC should be considered as a prehospital therapy. METHODS: A postal questionnaire was used to determine the current level of use of prehospital activated charcoal by ambulance NHS trusts, the incidence of associated complications, and barriers preventing the routine use of prehospital SDAC. RESULTS: A completed questionnaire was returned by 36 of the 39 ambulance NHS trusts in the UK (response rate 92%). Currently none of the trusts that responded to the questionnaire provides prehospital SDAC as an intervention. The most common barriers to the provision of prehospital SDAC are the current lack of evidence in the medical literature proving it is effective in improving patient outcome and the lack of a recognised protocol for its administration. Other issues included concerns regarding potential complications, ambulance turnaround times, lack of availability of SDAC, and lack of funding. CONCLUSIONS: A lack of published evidence proving efficacy remains the most important factor in preventing the routine administration of SDAC to appropriate patients in the prehospital environment. Further research in this setting is required to determine the usefulness of this therapy.

Acute poisoning: understanding 90% of cases in a nutshell.

The acutely poisoned patient remains a common problem facing doctors working in acute medicine in the United Kingdom and worldwide. This review examines the initial management of the acutely poisoned patient. Aspects of general management are reviewed including immediate interventions, investigations, gastrointestinal decontamination techniques, use of antidotes, methods to increase poison elimination, and psychological assessment. More common and serious poisonings caused by paracetamol, salicylates, opioids, tricyclic antidepressants, selective serotonin reuptake inhibitors, benzodiazepines, non-steroidal anti-inflammatory drugs, and cocaine are discussed in detail. Specific aspects of common paediatric poisonings are reviewed.

Powdery Mildew Caused by an Oidium sp. on Twenty-One Annual Medicago spp. in California.

Powdery mildew was observed in plots of USDA Plant Introduction accessions of medic plants grown for seed increase at Riverside, CA, from 1995 to 1998. White, diffuse to dense, amphigenous mycelia bearing Oidium conidia appeared on shoots in April each year and remained active until the last plants matured in June. Invaded leaflets became necrotic and dropped prematurely, sometimes leaving a green petiole. However, mildew incidence was low in most plots, and symptomless plants occurred in all species. Conidia were ellipsoid-cylindrical and measured 15 to17 × 39 to 47 µm. A sexual state of the fungus was not observed. Morphological characteristics of the anamorph matched those of Erysiphe pisi (1). In growth chambers, conidia from medic plants caused severe mildew of garden pea (Pisum sativum L. 'Early Perfection'). Powdery mildew occurred in plots of Medicago ciliaris, M. constricta, M. coronata, M. disciformis, M. doliata, M. granadensis, M. intertexta, M. italica, M. lesinsii, M. littoralis, M. lupulina, M. minima, M. murex, M. noeana, M. orbicularis, M. rigidula, M. rotata, M. rugosa, M. scutellata, M. truncatula, and M. turbinata. We believe this is the first report of naturally occurring powdery mildew on these species in the United States. Reference: (1) H. J. Boesewinkel. Bot. Rev. 46:167, 1980.

An observational study of isotretinoin recipients treated for acne in a health maintenance organization.

From September 1982 to June 1987, all members (N = 513) of the Group Health Cooperative of Puget Sound, Seattle, Wash, who were prescribed isotretinoin for acne were observed throughout the first 4- to 5-month course of therapy for effectiveness and adverse effects. The highest rates of use were among male subjects aged 15 to 24 years. Excluding 47 subjects whose prescriptions were stopped because of noncompliance or who left the care of Group Health Cooperative physicians, 39 (8.4%) of the remaining 466 discontinued taking the drug because of the following adverse effects: mucous/skin/musculoskeletal effects (17); elevated triglyceride levels (eight); headaches (five); increased liver enzyme levels (three); amenorrhea (two); and other (four). One subject, excluded from the 466 because of noncompliance, became pregnant while using medication from a previous prescription and had a therapeutic abortion; she was not under the care of a physician at the time of pregnancy. Most subjects (97%) developed a mucocutaneous symptom, and 42% developed musculoskeletal symptoms. Moderate elevations in liver enzyme levels developed in six (1.8%) of 341 subjects with normal baseline values. Of 389 subjects with normal baseline triglyceride values (less than 2.25 mmol/L), nine (2.3%) developed moderate elevations (4.5 to 9.0 mmol/L), and one (0.3%) developed a severe elevation (greater than or equal to 9.0 mmol/L). Of 24 subjects with elevated baseline triglyceride levels, three (12.5%) developed moderate elevations. Of an additional 53 subjects whose baseline serum triglyceride levels were not determined, two developed elevations during therapy, one up to 13.4 mmol/L. Subjects who were overweight or had elevated baseline serum triglyceride values had an increased risk of developing elevations in triglyceride levels during therapy (odds ratio, 6.0; 95% confidence interval, 1.6 to 22.0; and odds ratio, 4.35; 95% confidence interval, 0.9 to 20.2, respectively). Acne was improved for at least 94.0% of subjects.

Variable expression in ankyloblepharon-ectodermal defects-cleft lip and palate syndrome.

The ankyloblepharon-ectodermal defects-cleft lip and palate (Hay-Wells) syndrome is a rare autosomal dominant form of congenital ectodermal dysplasia. It is characterized by coarse, wiry, sparse hair; dystrophic nails; slight hypohidrosis; scalp infections; ankyloblepharon filiforme adnatum; hypodontia; maxillary hypoplasia; and cleft lip and palate. To date, 12 patients have been reported; however, the diagnosis has been questioned in 3 of these patients. We report 2 additional patients, one of whom has nasal speech but not cleft palate, in contrast to all other reported patients. This entity must be distinguished from numerous other forms of ectodermal dysplasia, especially those forms that can be associated with oral clefts and/or ankyloblepharon.

Effect of stimulus configuration on spatial judgments in search tasks.

Although children over one year of age are able to code spatial information with respect to objects other than the self, there are many instances in which the self is inappropriately used as a spatial referent by children between 2 and 4 years of age. L. G. Braine and R. A. Eder (1983, Developmental Psychology, 19, 45-55) found that, in a search task, the nature of the array influenced the spatial referent used by 2-year-old children. The present work investigated the effect of varying the number, size, and arrangement of boxes in the array. It was found that only the number of boxes defining the left and right sides of the array influenced performance; that is, multiple boxes were associated with the use of external objects as spatial referents. These results were interpreted as stemming from the tendency of young children to code the location of an object with respect to nearby objects. This tendency would lead to the use of adjacent boxes and environmental objects as spatial referents for the multiple-box side, and the use of the self as a spatial referent for the single-box side.

Mass spectral investigations on trichothecene mycotoxins. II. Detection and quantitation of macrocyclic trichothecenes by gas chromatography/negative ion chemical ionization mass spectrometry.

A general, sensitive gas chromatographic/negative ion chemical ionization mass spectrometric (GC/NICIMS) method of analysis was developed for the detection and quantitation of several polar, thermally labile, toxic macrocyclic trichothecenes. The procedure involves the conversion of the molecules to their corresponding alcohols (verrucarols) by alkaline hydrolysis, followed by derivatization of the hydrolysate with heptafluorobutyrylimidazole and analysis by GC/MS technique under negative ion chemical ionization conditions. Nanogram (250 ng) quantities of several macrocyclic trichothecenes with different verrucarol and ester moieties were analyzed successfully with good precision by this procedure. The method was applicable for the accurate determination of at least low ppb levels of these macrocyclic trichothecenes in environmental samples, such as fungal products, fermentation broths, and plant samples. This is the first reported, well developed, sensitive, and applicable method for the detection and quantitation of these compounds in naturally occurring samples.

Bullous morphea profunda.

A deep sclerotic process developed on the shins of a 58-year-old man, and eosinophilic fasciitis or morphea profunda was suspected clinically. Bullae later arose on the plaques, and histologic examination of a skin biopsy specimen revealed sclerosis and inflammation of the deep dermis, panniculus, and fascia, with subepidermal edema causing formation of bullae. No lymphatic obstruction or vasculitis was seen. Two plaques of typical morphea on the penis were noticed 10 months later. The patient had no peripheral or tissue eosinophilia, hypergammaglobulinemia, hematologic abnormality, or history of exertion before the onset of the disease. The sclerotic process involved more than the fascia. In describing this deeper variant of morphea, the term "morphea profunda" appears to be more appropriate than "eosinophilic fasciitis."

Netherton's syndrome. Report of a case and review of the literature.

A patient with Netherton's syndrome who was followed since birth had previously been diagnosed as having Leiner's disease and acrodermatitis enteropathica; the disorder was recognized clinically when the patient was 20 years of age. Therapy with 13-cis-retinoic acid significantly aggravated the ichthyosis and induced increased fragility of the skin. This patient also had an intermittent aminoaciduria with clinical investigations that showed normal renal function. Furthermore, the aminoaciduria resolved spontaneously after the discontinuance of topically applied corticosteroids. The normal results of clinical studies and a review of the literature suggest that the aminoaciduria may have been artifactual because excess absorption of topically applied corticosteroids directly affects the renal tubules and impairs renal reabsorption or enhances the free excretion of amino acids. We review forty-two other cases of Netherton's syndrome in the literature and reaffirm the significance of associated ichthyosis, atopy, trichorrhexis invaginata, and other findings in this unique syndrome.

Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria.

Fifty patients with chronic idiopathic urticaria were studied to compare responses to treatment with doxepin (10 mg three times a day) and with diphenhydramine (25 mg three times a day). All patients had an evaluation that failed to disclose a cause for their disease. Therapeutic response was assessed according to the suppression of symptoms and symptom diary scores of daily itching and frequency, number, size, and duration of hives. Total clearing of the pruritus and urticarial lesions occurred in 43% of the patients while receiving doxepin and in only 5% while receiving diphenhydramine (p less than 0.001). Partial or total control of the pruritus and hives was noted in 74% of the patients receiving doxepin and in only 10% of those receiving diphenhydramine (p less than 0.001). Doxepin induced markedly less sedation (22%) than diphenhydramine (46%) (p less than 0.05). Dermatopathologic categories included (1) urticaria simplex, (2) lymphocytic urticaria, and (3) leukocytoclastic urticaria. Patients with urticaria simplex had a more favorable response to doxepin than the two other groups.