National toxicovigilance for pesticide exposures resulting in health care contact - An example from the UK's National Poisons Information Service.

BACKGROUND: Although there are extensive systems in place for pharmacovigilance, similar systems for detecting adverse health effects relating to pesticide exposure are rare. In 2004, the National Poisons Information Service (NPIS) pesticide surveillance study was implemented to identify cases requiring health care contact in the UK. This report describes the epidemiology of pesticide exposures reported to poison centres in the UK over a 9-year period. METHODS: Data on exposures were gathered through monitoring access to the NPIS's online clinical toxicology database TOXBASE(®) and through monitoring calls to the four NPIS units (Edinburgh, Cardiff, Newcastle and Birmingham). Severity was judged by both caller and NPIS staff. RESULTS: During the 9 years, 34,092 enquiries concerning pesticides were recorded; 7,804 cases of pesticide exposure were derived from these enquiries. Exposures were predominantly unintentional and acute (6,789; 87.0%); 217 (2.8%) and 755 (9.7%) were chronic unintentional and acute deliberate self-harm exposures, respectively. The majority of cases occurred in children, especially the 0-4 year age group The minimum incidence of pesticide exposure requiring health care contact was 2.0 cases/100,000 population per year. Reported numbers were 6- to 25-fold greater than those picked up through other UK pesticide toxicovigilance schemes. There were 81 cases of severe toxicity and 38 cases of fatal exposure. Deliberate self-harm accounted for 62.3% of severe cases and 79% of deaths. Aluminium phosphide, paraquat, diquat and glyphosate were responsible for most severe and fatal cases. CONCLUSIONS: The data gathered from this pesticide surveillance study indicate that poison centre resources can usefully monitor pesticide exposures resulting in health care contact in the UK. The NPIS may usefully be one component of the UK's response to European legislation requiring surveillance of complications resulting from pesticide use.

The use of atropine in a nerve agent response with specific reference to children: are current guidelines too cautious?

This review examines the potential use of nerve agents by a terrorist organisation against a civilian population, which has become an increasingly apparent threat in the UK. Present guidelines for the use of atropine, particularly in children, following such an event are unclear. No precise agreement exists on the most appropriate dose of atropine, or the frequency with which it should be administered. This uncertainty leaves children vulnerable as potentially life-saving treatment may be crucially delayed. Guidelines must be standardised to allow rapid antidotal delivery and maximise the potential for survivors. This review examines the issues currently surrounding the use of atropine in children following a nerve agent attack and propose strategies for treating exposed children.

Interpretation of clinical guidelines for poisoned patients: positive and negative effects of standard phrases used in TOXBASE.

INTRODUCTION: Electronic information sources are increasingly relied upon for clinical management advice. TOXBASE is a standardised online resource that offers clinical advice on the management of poisoned patients and is the first point of contact between clinicians and the National Poisons Information Service in the United Kingdom. Advice is delivered using a series of standard phrases. The present study examined how healthcare professionals interpret the phrases and studied their impact on clinical decision-making. METHODS: A structured prospective written questionnaire was offered to healthcare staff in the Lothian region, and an electronic questionnaire issued to TOXBASE users across the United Kingdom. Participants were asked to respond to a variety of scenarios representing acutely poisoned patients. Clinical management advice was offered via TOXBASE using a variety of standard phrases, and participants were asked to express the likelihood that they would then administer gut decontamination treatment. RESULTS: There were 70 respondents to written questionnaires, and 119 respondents to the electronic version. Phrases that included didactic instructions, for example 'give', 'contraindicated', 'do' and 'perform' were associated with strongly positive or strongly negative responses. In contrast, advice that consisted of open phrases such as 'consider', 'benefit uncertain', and 'few data' were associated with inconsistent responses. CONCLUSION: Didactic words and phrases are associated with more consistent interpretation and response than open-ended words and phrases. The choice of words and phrases used in electronic systems can have an independent impact on clinical decision-making and require further consideration.

UK childhood exposures to pesticides 2004-2007: a TOXBASE toxicovigilance study.

OBJECTIVE: There are no systematic methods for toxicovigilance of non-medicinal products in the UK. This is particularly relevant for pesticides, where there is significant public concern about potential adverse effects. This study describes a prospective toxicovigilance scheme based on follow-up of enquiries to the National Poisons Information Service (NPIS) through its online poisons information system TOXBASE. These enquiries reflect acute exposures and the patterns of acute illness that result. RESULTS: A total of 10 061 pesticide-related enquiries were identified. After follow-up, data were gathered on 2364 suspected exposures, of which 1162 involved children. After exclusions, 1147 exposures are reported here. No deaths were reported and only 37 children were admitted to hospital. The majority were considered to have either minimal or no features (925, 80.6%). Symptoms for 38 children were unknown. Symptoms reported in the other 184 children included nausea or vomiting (58), eye irritation, pain or conjunctivitis (29), skin irritation (28), abdominal pain (24), mouth or throat irritation (18) and diarrhoea (15). Where age was recorded, 60.5% (680) of children involved in suspected pesticide exposures were aged 2 years or less. The most common scenario for acute accidental exposure to pesticide in children was exposure after application (329, 28.7%) or due to poor storage (228, 19.9%). CONCLUSIONS: Areas of potential concern identified included storage, access of young children to "laid" baits and pesticides, and exposures as a result of medication errors, with liquid head lice preparations being confused with other medicines. Use of NPIS systems provides a potentially useful method of toxicovigilance.

Acute caffeine ingestion: clinical features in patients attending the emergency department and Scottish poison centre enquiries between 2000 and 2008.

BACKGROUND AND AIMS: Little information is available regarding the healthcare burden associated with deliberate caffeine ingestion. The present study sought to establish the impact of caffeine ingestion on hospital attendances and Poisons Centre enquiries in Scotland. METHODS: Retrospective analyses of clinical data from patients attending the Royal Infirmary of Edinburgh after acute caffeine ingestion, and TOXBASE enquiries from Scotland regarding caffeine poisoning between 2000-2008 inclusive. Cochran-Armitage trend tests were used to evaluate changes in annual admissions and TOXBASE enquiries. RESULTS: There were 43 hospital attendances due to deliberate caffeine ingestion, representing 0.2% of all poisoning cases. The median (interquartile range) stated dose was 1040 mg (600-1500 mg). Minor gastrointestinal symptoms were common, and no patient developed features of severe toxicity. There were 1418 enquiries to TOXBASE concerning caffeine poisoning, representing 0.2% of all poisoning enquiries from Scotland. The proportions of hospital admissions and TOXBASE enquiries due to caffeine ingestion have remained constant. CONCLUSION: Caffeine ingestion is uncommon, and results in only a small number of hospital attendances and Poisons Centre enquiries. In contrast to patterns reported elsewhere, the prevalence of caffeine abuse has not increased in Scotland over recent years.

Survey of cases of paracetamol overdose in the UK referred to National Poisons Information Service (NPIS) consultants.

BACKGROUND: Paracetamol is the most common means of drug overdose in the UK. Guidance on management is available to junior doctors through TOXBASE, the online resource managed by the UK National Poisons Information Service (NPIS) and in poster form. TOXBASE is supported by NPIS units and further by a UK national rota of clinical toxicologists. A study was undertaken to examine reasons why calls about paracetamol are referred to consultants to better understand issues in managing this common poisoning. METHODS: Calls relating to paracetamol overdose referred by a poisons information specialist to the duty NPIS consultant between 1 May 2005 and 30 April 2006 were identified from the database and the number of TOXBASE accesses during the same time period was determined. Enquiries that resulted in consultant referral were classified into six categories. RESULTS: Calls referred to NPIS consultants pertain mainly to patients who present late, staggered overdoses, adverse reactions to N-acetylcysteine, and interpretation of blood results. This information has been used to inform the development of TOXBASE so that comprehensive advice is readily available to end users. CONCLUSIONS: The operation of a national consultant rota enables information on difficult or unusual cases of poisoning to be pooled so that treatment guidelines can be developed to optimise treatment throughout the UK.

Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit.

BACKGROUND: Lithium toxicity may result in severe clinical features. There is on-going uncertainty about the significance of serum lithium concentrations in patients with lithium toxicity. AIM: To examine potential relationships between stated quantity of lithium ingested, serum lithium concentrations, and poisoning severity among patients referred to a regional poisons centre. METHODS: Prospective evaluation of enquiries to the Scottish Poisons Information Bureau about lithium toxicity between 2000-2005 inclusive. RESULTS: There were 172 enquiries, relating to acute ingestion (n = 101), acute-on-therapeutic ingestion (n = 38), or chronic poisoning (n = 33). Poisoning severity was moderate or severe in 9.9%, 26.3% (p < 0.05 vs. acute) and 54.5% (p < 0.005 vs. acute) of each group, respectively. Median (IQR) serum lithium concentrations in each group were: 2.4 (1.7-3.3) mmol/l, 2.1 (1.4-3.8) mmol/l, and 2.3 (1.9-3.3) mmol/l, respectively. The median stated quantities ingested in acute and acute-on-therapeutic lithium exposure were 5000 mg (2000-11 050 mg) and 4000 mg (2400-8820 mg), respectively. DISCUSSION: Patients with acute-on-therapeutic and chronic poisoning are at greatest risk of severe toxicity. These differences cannot be explained by either the quantity of lithium ingested or serum lithium concentration alone.

Five years of poisons information on the internet: the UK experience of TOXBASE.

INTRODUCTION: In 1999, the UK adopted a policy of using TOXBASE, an internet service available free to registered National Health Service (NHS) departments and professionals, as the first point of information on poisoning. This was the first use worldwide of the internet for provision of clinical advice at a national level. We report the impact on database usage and NPIS telephone call loads. METHODS: Trends in the pattern of TOXBASE usage from 2000-2004 are reported by user category. Information on the monographs accessed most frequently was also extracted from the webserver and sorted by user category. The numbers of telephone calls to the National Poisons Information Service (NPIS) were extracted from NPIS annual reports. RESULTS: Numbers of database logons increased 3.5 fold from 102,352 in 2000 to 368,079 in 2004, with a total of 789,295 accesses to product monographs in 2004. Registered users increased almost tenfold, with approximately half accessing the database at least once a year. Telephone calls to the NPIS dropped by over half. Total contacts with NPIS (web and telephone) increased 50%. Major users in 2004 were hospital emergency departments (60.5% of logons) and NHS public access helplines (NHS Direct and NHS24) (29.4%). Different user groups access different parts of the database. Emergency departments access printable fact sheets for about 10% of monographs they access. CONCLUSION: Provision of poisons information by the internet has been successful in reducing NPIS call loads. Provision of basic poisons information by this method appears to be acceptable to different professional groups, and to be effective in reducing telephone call loads and increasing service cost effectiveness.

Co-proxamol overdose is associated with a 10-fold excess mortality compared with other paracetamol combination analgesics.

AIMS: To assess the relative toxicity of co-proxamol in overdose in comparison to the 2 other paracetamol-opioid combination products, co-codamol and co-dydramol. METHODS: Data collected over a 2-year period (July 2000-June 2002) was used to estimate the frequency of overdose and death for the three most popular paracetamol-opioid compound analgesics. Prescription data for Scotland and Edinburgh, the number of overdoses (derived from overdose admissions in Edinburgh) or Poisons Information Service contacts in Scotland, and national death records were used to calculate a series of indicators relating morbidity (admissions), surrogates of morbidity (poisons enquiries by telephone or internet) and mortality to prescriptions. RESULTS: When related to prescription volume overdoses involving co-proxamol in Scotland were 10 times more likely to be fatal (24.6 (19.7, 30.4)) when compared with co-codamol (2.0 (0.88, 4.0)) or co-dydramol (2.4 (0.5, 7.2)). In contrast there was no difference in the presentation rate or enquiry rates for these analgesics when corrected for prescriptions. CONCLUSIONS: The excess hazard from co-proxamol is due to inherent toxicity rather than increased use in overdose. We estimate from this study that withdrawal of co-proxamol would prevent 39 excess deaths per annum in Scotland alone.

Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose?

OBJECTIVE: To investigate likelihood of self-harm by overdose with antidepressant drugs of different types by examining hospital admission data and poisons inquiries and relating them to prescribing. DESIGN: Retrospective analysis of prospectively collected data on overdose admissions, poisons inquiries and prescribing of antidepressants in Edinburgh and Scotland. SETTING: Poisons treatment unit of the Royal Infirmary of Edinburgh and its surrounding catchment for overdose cases and Scotland for poisons inquiries. PARTICIPANTS: All patients admitted to the Royal Infirmary of Edinburgh between 1 January 2000 and 31 December 2002 with an overdose involving an antidepressant. MAIN OUTCOME MEASURES: Overdose admissions (patients) in relation to prescribing in Edinburgh and poisons inquiries in relation to prescription rates in Scotland. RESULTS: There were 1656 admissions involving 1343 patients. The likelihood of admission for an individual patient in relation to volume of prescribing (likelihood ratio: 95%CI) in the catchment was somewhat smaller for amitriptyline (0.83:0.74-0.92) and sertraline (0.79:0.63-0.99), and somewhat greater for mirtazapine (1.99:1.57-2.51), trazadone (1.30:1.09-1.54) and venlafaxine (0.97:1.81-1.16) [corrected] For poisons inquiries in Scotland, the excess for venlafaxine and mirtazapine was confirmed and likelihood of an inquiry lowest for selective serotonin re-uptake inhibitors (SSRIs). CONCLUSIONS: There was no evidence of an excess likelihood of presentation with overdose with SSRIs, and the likelihood was reduced with sertraline. There was a small excess of both admissions and poisons inquiries for mirtazapine and venlafaxine. This is a concern in view of the increased toxicity of venlafaxine in overdose in comparison with SSRIs.

Comparative toxicity of citalopram and the newer antidepressants after overdose.

OBJECTIVE: To compare the toxicity of citalopram, venlafaxine, mirtazapine, and nefazadone after overdose. METHODS: Two-year retrospective review of consecutive patients admitted to the toxicology unit of Edinburgh Royal Infirmary. Outcome measure included physiological variables, ECG recordings, peak creatine kinase, development of arrhythmias, seizure, tremor or agitation, and the need for admission to a critical care facility. RESULTS: A total of 225 patients were studied. Venlafaxine was associated with a significantly higher pulse rate (p < 0.0001) and tremor (p = 0.007) than other antidepressants. Citalopram was associated with a significantly longer QT interval on ECG recording (p < 0.0001) but mean QTc durations were not significantly different between all drugs studied. No arrhythmias were recorded. Only venlafaxine and citalopram caused seizures and were associated with the need for admission to Intensive Care, but there was no significant difference between them. CONCLUSIONS: Mirtazapine and nefazadone appear safe in overdose and were associated with minimal features of neurological or cardiovascular toxicity. Citalopram is more likely to cause QT prolongation but other features of cardiovascular toxicity were uncommon. Both citalopram and venlafaxine are proconvulsants. Venlafaxine also causes more frequent features of the serotonin syndrome.

Quinine intoxications reported to the Scottish Poisons Information Bureau 1997-2002: a continuing problem.

Quinine is widely prescribed in the UK for night cramps. Its potential toxicity in overdose is well known. We have reviewed the Scottish experience of enquiries regarding quinine overdose to the poisons information service responsible for Scotland over a 6-year period. Between 1997 and 2002 there were 96 reports of suspected quinine toxicity from Scotland (population 5.2 million), 19 of which were in children. The largest quantities of drug ingested were in patients between the ages of 11 and 30. In comparison with older studies the pattern of quinine poisoning does not appear to have changed in the UK over 20 years, despite recognition that it is a toxic agent in overdose, and particularly in children.

Effects of licence change on prescribing and poisons enquiries for antipsychotic agents in England and Scotland.

AIMS: To examine the effect of licence change for thioridazine at the end of 2000 on the prescription of antipsychotic drugs in England and Scotland, and investigate changes in poisons information inquiries and, for Edinburgh, poisons admissions. METHODS: Prescription data for antipsychotic drugs were obtained for England and Scotland and quarterly trends examined for 2000 and 2001. Accesses to the UK National Poisons Information Service website TOXBASE for antipsychotic products were examined for the same period. For Scotland telephone enquiry data, and admission data to the Edinburgh Poisons Unit were also evaluated. Trends in poisonings were compared with prescribing change. RESULTS: In England prescriptions for thioridazine fell rapidly in 2001 from approximately 35% of market share to less than 5%, and were replaced by risperidone, chlorpromazine and olanzapine. TOXBASE accesses fell from 39.3% of antipsychotics to 4.4%. Accesses for chlorpromazine, olanzapine and risperidone increased. In Scotland prescribing of thioridazine was similar to changes in England, but it was principally replaced by chlorpromazine. These changes were mirrored by TOXBASE accesses, telephone enquiries and in-patient admissions. The ratio of TOXBASE accesses for thioridazine to prescription numbers for the drug increased after the licence change. CONCLUSIONS: Licence change produced rapid change in prescribing behaviour within 3 months. Prescribing behaviour in England and Scotland was different. Changes in prescribing were mirrored by changes in accesses for poisons information in both England and Scotland, and in Edinburgh by hospital admissions. The increase in the ratio of TOXBASE accesses to prescriptions for thioridazine suggests doctors may have become more aware of its potential toxicity.

TOXBASE: poisons information on the internet.

OBJECTIVES: To assess the uptake, usage and acceptability of TOXBASE, the National Poisons Information Service internet toxicology information service. METHODS: An observational study of database usage, and a questionnaire of users were undertaken involving users of TOXBASE within the UK between August 1999, when the internet site was launched, and May 2000. The main outcome measures were numbers of registered users, usage patterns on the database, responses to user satisfaction questionnaire. RESULTS: The number of registered users increased from 567 to 1500. There was a 68% increase in accident and emergency departments registered, a 159% increase in general practitioners, but a 324% increase in other hospital departments. Between January 2000 and the end of May there had been 60 281 accesses to the product database, the most frequent to the paracetamol entry (7291 accesses). Ecstasy was the seventh most frequent entry accessed. Altogether 165 of 330 questionnaires were returned. The majority came from accident and emergency departments, the major users of the system. Users were generally well (>95%) satisfied with ease and speed of access. A number of suggestions for improvements were put forward. CONCLUSIONS: TOXBASE has been extensively accessed since being placed on the internet (http://www.spib.axl.co.uk). The pattern of enquiries mirrors clinical presentation with poisoning. The system seems to be easily used. It is a model for future delivery of treatment guidelines at the point of patient care.

Eye drops--the hidden poison.

Eye drops are very commonly prescribed but their potential for systemic absorption and serious toxicity may be forgotten. This paper examines patterns of prescription of eye drops in Scotland by general practitioners. A review of the serious systemic features and toxicity, and their management, of commonly used eye drops is undertaken. Practical recommendations for the monitoring of such effects in clinical practice are made.