John A Henry

Screening and referral for brief intervention of alcohol-misusing patients in an emergency department: a pragmatic randomised controlled trial.

BACKGROUND Alcohol misuse is highly prevalent among people attending emergency departments, but the effect of intervention by staff working in these departments is unclear. We investigated the effect of screening and referral of patients found to be misusing alcohol while attending an emergency department. METHODS We undertook a single-blind pragmatic randomised controlled trial. Patients received either an information leaflet or an information leaflet plus an appointment with an alcohol health worker. Outcome data were collected by patient interview and examination of hospital records at 6 and 12 months. FINDINGS 599 patients were randomised over a 12-month period. At 6 months, those referred to an alcohol health worker were consuming a mean of 59.7 units of alcohol per week compared with 83.1 units in the control group (t -2.4, p=0.02). At 12 months those referred were drinking 57.2 units per week compared with 70.8 in controls (t -1.7, p=0.09). Those referred to the alcohol health worker had a mean of 0.5 fewer visits to the emergency department over the following 12 months (1.2 compared with 1.7, t -2.0, p=0.046). Differences in quality of life were not found. INTERPRETATION Opportunistic identification and referral for alcohol misuse in an emergency department is feasible, associated with lower levels of alcohol consumption over the following 6 months, and reduces reattendance at the department. Short-term reductions in alcohol consumption associated with referral for brief intervention for alcohol misuse benefit patients and reduce demand for accident and emergency department services.

Low-dose MDMA (“ecstasy”) induces vasopressin secretion

p=0·025, one tail). Mean initial cortisol concentration was 331·4 nmol/L (range 208·8–603·4 nmol/L), which increased, although not significantly (p>0·05), to 377·2 nmol/L (range 268·4–583·3 nmol/L) at 2 h. Street “ecstasy” frequently contains more than 100 mg of MDMA. In this study, a single relatively small dose caused an acute rise in AVP concentration at a time of day when it would not be expected to change. The rise in AVP was accompanied by a small fall in plasma sodium concentrations. The hyponatraemic illness experienced by some users is thus likely to be linked to the drug’s ability to stimulate secretion of AVP. Hence, if fluid intake is excessive, even a relatively small dose of MDMA could lead to symptoms of hyponatraemia. The rise in AVP does not seem to be part of a generalised stress response because there was no significant change in plasma cortisol concentration. It therefore seems that MDMA-induced hyponatraemia is unlikely to be due to a rare and idiosyncratic reaction, but results from a pharmacological effect compounded by excessive fluid ingestion. Animal studies show that MDMA stimulates the output of serotonin by serotonergic neurones, and AVP secretion is regulated by serotonergic pathways. The message is that those who take “ecstasy” or similar drugs may be at risk of hyponatraemia and should, therefore, avoid drinking fluid in excess of the body’s requirements. This may be difficult for users to estimate because MDMA reduces perception of thirst and impairs judgment.

Injecting drug use in Brighton, Liverpool, and London: best estimates of prevalence and coverage of public health indicators

Study objective: To estimate the prevalence of injecting drug use (IDU) in three cities in England and to measure the coverage of key public health indicators. Design: Capture-recapture techniques with covariate effects. Setting: Liverpool, Brighton, and 12 London boroughs, 2000/01. Participants: IDU collated and matched across five data sources—community recruited survey, specialist drug treatment, arrest referral, syringe exchange, and accident and emergency—896 in Brighton, 1224 in Liverpool, and 6111 in London. Main results: It is estimated that in 2000/01 the number and prevalence of IDU aged 15–44 was 2300 (95%CI 1500 to 3700) and 2.0% (95%CI% 1.3% to 3.2%) in Brighton; 2900 (95%CI 2500 to 5000) and 1.5% (95%CI 1.3% to 2.6%) in Liverpool; 16 700 (95%CI 13 800 to 21 600) and 1.2% (95%CI 1.0% to 1.6%) in 12 London boroughs; with a prevalence of 1.7% (95%CI 1.2% to 3.3%) in inner London. It is estimated that: less than one in four IDU are in treatment in the three areas; syringe exchange programmes covered about 25% of injections in Brighton and Liverpool and 20% in London; and that the annual opioid mortality rate among IDU was 2% in Brighton compared with less than 1% in Liverpool and London. Conclusions: Credible estimates of the prevalence of injecting drug use (and key public health indicators) can be determined using covariate capture-recapture techniques. These suggest that: targets to double the number in treatment are possible: syringe distribution should be increased; and further attention, especially in Brighton, given to reducing overdose mortality.

Comparing cannabis with tobacco.

Britain now has 13 million tobacco smokers. This number has been steadily decreasing due to public awareness of the harm caused by tobacco smoking. At the same time the number of cannabis smokers is increasing. Between 1999 and 2001, the number of 14–15 year olds who had tried cannabis rose from 19% to 29% in boys and 18% to 25% in girls, and a Home Office document estimates that 3.2 million people in Britain smoke cannabis. 1 2 However, the harmful effects of smoking cannabis are widely known and have recently been highlighted. 3 4 Although the active ingredients of the cannabis plant differ from those of the tobacco plant, each produces about 4000 chemicals when smoked and these are largely identical. Although cannabis cigarettes are smoked less frequently than nicotine cigarettes, their mode of inhalation is very different. Compared with smoking tobacco, smoking cannabis entails a two thirds larger puff …

Action of MDMA (Ecstasy) and Its Metabolites on Arginine Vasopressin Release

Abstract: 3,4‐Methylenedioxymethamphetamine (MDMA) has been reported to cause hyponatraemia, which appears to result from inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). After administration of a low dose of (R,S)‐MDMA (40 mg) to eight healthy drug‐free male volunteers, concentrations of AVP in plasma increased significantly at 1, 2, and 4 hours. Although no relation between plasma MDMA and AVP was found on an examination of the entire data set over the 24‐hour study period, a statistically significant negative correlation was observed at 1 hour. As this occurred at a time when both AVP and MDMA concentrations were rising, it was postulated that a metabolite, or metabolites, could primarily be responsible for the increase in AVP. To test this hypothesis we examined the effect of MDMA and five of its metabolites, in the dose range 0.1‐1,000 nM, on AVP release from the isolated rat hypothalamus. All compounds tested were found to increase AVP release (using 10 nM and 1,000 nM concentrations), with 4‐hydroxy‐3‐methoxymethamphetamine (HMMA), the major metabolite of MDMA, being the most potent, and 3,4‐dihydroxymethamphetamine (DHMA) the least potent. Each compound (1,000 nM), with the exception of DHMA, also enhanced the response to 40‐mM potassium stimulation. Our findings confirm that metabolites of MDMA, in addition to the parent drug, contribute to AVP secretion in vitro. Further work will demonstrate whether this is also true in vivo.

Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine (“ecstasy”): is metabolism a contributory factor?

The aim of this investigation was to examine the effect of 3,4‐methylenedioxymethamphetamine (MDMA) administration on arginine vasopressin (AVP) release. (R,S)‐MDMA (40 mg) was administered to eight normally hydrated healthy male volunteers (22–32 years) and blood samples were collected up to 24 h. Plasma was assayed for AVP and cortisol by radioimmunoassays, and for MDMA and the N‐demethylated metabolite, MDA, by gas chromatography‐mass spectrometry. Sodium concentrations and osmolality were also determined. Plasma AVP increased in all subjects after MDMA administration and a significant negative correlation was observed between concentrations of AVP and both single and total enantiomer MDMA at 1 h (r < −0.91, P < 0.01). This had disappeared by 2 h (P > 0.7). Compared with basal values, no significant change was observed for osmolality or cortisol at 1 h after drug administration. In conclusion, plasma AVP concentrations increase after MDMA administration, but the increase is not part of a generalized stress response since cortisol did not increase concurrently. A significant negative correlation between plasma MDMA and AVP was observed soon after administration. The possibility that a pharmacological effect of MDMA is primarily mediated via one or more metabolites, rather than by the parent drug, should be considered.

Overdose profiles of new antipsychotic agents.

Although the more recently introduced antipsychotic drugs are increasing in popularity, the pattern of symptomatology when taken in overdose is not well defined. We monitored all enquiries to the National Poisons Information Service, London (NPIS, London) concerning antipsychotic drugs over a 9-month period in 1997 and report our findings concerning four drugs (olanzapine, clozapine, risperidone and sulpiride). All overdoses involving a single agent were followed up by a letter to the enquirer requesting details and outcome of the case. Although a total of 574 enquiries involving the selected antipsychotic drugs were received, only 45 of these cases involved overdose with a single agent. There were no fatalities or cases of convulsions in the series. Cardiac arrhythmias were only noted with sulpiride. Symptoms were most marked with clozapine, with a majority of patients experiencing agitation, dystonia, central nervous system (CNS) depression and tachycardia. Olanzapine and sulpiride produced a range of different symptoms, while most patients who had taken risperidone were asymptomatic. Monitoring poisons centre enquiries is a useful way of comparing overdose toxicities. We conclude that at least two of the novel antipsychotic agents, olanzapine and risperidone, appear to have a favourable overdose profile, which suggests that they are safer in overdose than the phenothiazines and butyrophenones.

Composition and toxicity of petroleum products and their additives

1 All petroleum based products are highly complex chemical mixtures. Although almost exclusively composed of hydrocarbons, the composition varies with the crude oil source. 2 Their toxicity for man is generally low but there are exceptions. Although irritancy and sensitization to specific ingredients may be demonstrated in animals, animal experiments are not a reliable indicator of sensitization potential in man. 3 Both product complexity and commercial considerations can make acceptable and meaningful compositional disclosures difficult. A nomenclature system exists which solves these problems. 4 Frame formulations would have some value to poisons centres dealing with petroleum product enquiries. 5 As legislation for the European Union is developed, the balance must be reached between disclosure of the (often confidential) precise chemical composition of products and a practical and useful composition for the guidance of users and medical personnel. This is a key issue with some petroleum products, mainly due to the additives used in them. 6 For several reasons, such as climatic conditions or logistics of supply, the various components, including additives, used in a branded product may vary because the final product composition is determined not by chemistry but by performance in service. 7 Lubricants may contain between 10 and 20% of additives; fuels contain additives only at parts per million levels. However, for both fuels and lubricants, toxicity from additives is rarely a matter of concern.

Assessment and management of acute poisoning by petroleum products.

Petroleum products are highly complex chemical mixtures consisting predominantly of hydrocarbons. Their composition varies with source and intended use of the product. Virtually all are blended products that come into contact with man in a wide range of circumstances. Their toxicity for man is generally low and the use of additives rarely affects the toxicity of the final product. Because products are blended to meet performance, and not chemical specifications, their composition varies significantly. Management of toxicity benefits from simplified guidelines that consider the product by its type. Management in most cases is symptomatic, but the doctor needs to be aware of the potential for development of sequelae such as aspiration pneumonia and central nervous system (CNS) depression. Local and systemic effects of exposure to hydrocarbons are reviewed, as are immediate assessment and recommended management of acute exposure to petroleum products. Because of the large scope of this subject, this paper limits itself to acute toxicity of petroleum products encountered inthe public domain. It does not address topics such as chronic toxicity, solvent abuse, petrochemicals, or pesticides.

The antidotal effect of α1-acid glycoprotein on amitriptyline toxicity in cardiac myocytes

Tricyclic antidepressants in overdose cause toxicity marked by prolongation of the QRS interval of the electrocardiogram. These drugs are bound to alpha(1)-acid glycoprotein (AAG) with high affinity in plasma. Animal studies have shown that the administration of AAG shortens the QRS prolongation induced by tricyclic antidepressants. In order to clarify the pharmacological mechanism involved and to obtain clinically relevant evidence at the cellular level, whole-cell patch clamp techniques were performed in single guinea-pig ventricular myocytes to elicit the time and voltage-dependent fast sodium currents using both normal and modified physiological solutions. Cells stayed viable for much longer when they were placed in normal physiological solutions, providing sufficient recording time for consistently reproducible, clinically relevant toxicological results to be obtained. Amitriptyline (AMI) produced a concentration-dependent blockade of sodium currents with an approximate IC(50) of 0.69 microM. AAG reversed this blockade in a concentration-dependent fashion at concentrations ranging from 3.2 to 12.8 microM. Using the same experimental conditions, AAG also reversed the blockade of sodium current by quinidine, a class I antiarrythmic drug. Albumin did not reverse the blockade of sodium channels by AMI. The results indicate that AAG is a potential antidote for tricyclic antidepressant overdose.