Effect of the UK Psychoactive Substances Act 2016 on episodes of toxicity related to new psychoactive substances as reported to the National Poisons Information Service. A time series analysis.

BACKGROUND: There have been recent increases in use of new psychoactive substances (NPS) associated with acute health harms including hospital presentations due to toxicity and increasing numbers of deaths. In response, the UK Government enacted generic legislation on 26th May 2016 (the Psychoactive Substances Act) making it an offence to produce, possess with intent to supply, supply, import or export, or possess within a custodial setting a psychoactive substance. We studied the impact of this Act on monthly frequency of enquiries made by health professionals to the UK National Poisons Information Service (NPIS) about NPS. We also studied five commonly used 'conventional' drugs of misuse that had been controlled prior to January 2009. METHOD: Anonymised clinical enquiries to the NPIS and accesses to the poisons information database TOXBASE were reviewed retrospectively from January 2009 to December 2018 to ascertain the trends in reported toxicity for NPS, cocaine, heroin, cannabis, amphetamines and MDMA. Data were analysed using interrupted time series analysis with the date of the PSA used as an independent predictor. RESULTS: Over the period of study there were 3,866 NPIS telephone enquiries and 79,271 TOXBASE user accesses made by UK health professionals concerning NPS. There were increases in monthly TOXBASE accesses (t = 7.408, P < 0.0001) and telephone enquiries (t = 4.74, P < 0.001) over the pre-specified period January 2009 to May 2016. Comparing the period after the PSA with that before, there were significant reductions in TOXBASE accesses (t = -3.327, P < 0.001) and telephone enquiries (t = -6.97, P < 0.001), although reductions started before May 2016. There were no significant changes for the five conventional drugs. There were significant reductions in telephone enquiries (t = -3.418, P < 0.001) and non-significant reductions in TOXBASE accesses (t = -1.713, P = 0.089) for NPS between June 2016 and December 2018. Increases in telephone enquiries for cocaine and reductions TOXBASE accesses for MDMA were also observed over that period. CONCLUSIONS: There have been significant recent reductions in NPIS enquiry activity relating to NPS; although these began before enactment of the PSA in May 2016.

Features reported after exposure to automatic dishwashing rinse aids.

INTRODUCTION: Automatic dishwashing rinse aids are drying aids which contain non-ionic surfactants, usually ethoxylated alcohols, typically at concentrations of ≤30%. OBJECTIVE: To assess the reported toxicity of rinse aids. METHODS: Telephone enquiries to the UK National Poisons Information Service were analysed from January 2008 to June 2019. RESULTS: Ingestion: Ingestion was involved in 976 cases and produced gastrointestinal features, coughing and central nervous system depression, particularly in young children. In those in whom the amount ingested was known, the majority (56%) of children <18 years and of adults (57%) ingested <50 mL of rinse aid. Although moderate or severe exposures (Poisoning Severity Score (PSS) ≥ 2) were uncommon, they occurred significantly (p < 0.0008) more often in adults (9.0%) than in children (1.8%); however, three of the four adults with PSS ≥ 2 co-ingested other substances. Eye exposure: Ocular exposure was reported in 35 cases, of whom 29 developed features. Eye irritation (n = 10, 28.6%) and eye pain (n = 10, 28.6%) were reported most commonly, and three patients (8.6%) developed corneal abrasions (PSS 2). Dermal exposure: Thirty-four patients were exposed dermally, and six (17.6%) reported features, including rash, numbness, pruritus and burns (PSS 1). CONCLUSIONS: Overall, clinical features developed in 47% of patients exposed to rinse aids, but more severe features (PSS ≥ 2) were rare (<3%) following exposure by any route.

Toxicity of traditional and soluble film automatic dishwashing tablets.

INTRODUCTION: Detergents used in automatic dishwashing machines are of two main types: traditional tablets that require removal from an external wrapper and newer soluble film tablets. OBJECTIVE: To determine the toxicity of automatic dishwashing tablets. METHODS: Telephone enquiries to the UK National Poisons Information Service were analysed for the period January 2008 to June 2019. RESULTS: Ingestion: Ingestion was involved in 798 traditional tablet exposures and 725 soluble film exposures. Clinical features (Poisoning Severity Score ≥ 1) developed in 22.2% of patients ingesting traditional tablets and in 28.8% ingesting soluble film tablets; moderate or severe toxicity was rare (<0.5% for both traditional and soluble film tablets). Children (≤5 years) significantly (p < 0.0001) more often developed features following ingestion of soluble film (n = 193, 28.2%) than traditional tablets (n = 134, 19.1%). In contrast, adults more often developed features following ingestion of traditional than soluble film tablets, although this difference was not statistically significant. Eye exposure: The eye was involved in only 26 of 1539 exposures; 17 of 26 exposures resulted in ocular features. The most commonly reported features were conjunctivitis, eye pain and blurred vision, although one patient sustained a corneal abrasion and developed loss of vision. Skin exposure: Thirty-four of 1539 exposures involved the skin but only 3 developed dermal features which were minor. CONCLUSIONS: Children (≤5 years) significantly more often developed features following ingestion of soluble film than traditional tablets, although the likelihood of a child developing features was relatively low (<30%) and features that did develop were almost always mild. In contrast, adults more often developed features following the ingestion of traditional than soluble film tablets. Overall, the eye was involved in only 1.7% of exposures and only one patient sustained a corneal abrasion.

Gabapentin and pregabalin: do the benefits outweigh the harms?

Gabapentin and pregabalin prescribing in Scotland has increased substantially over recent years. Evidence suggests that prescribers may be advocating the use of these medicines off-label to avoid prescribing opioid analgesics. The evidence to support gabapentin and pregabalin use in non-neuropathic pain disorders indicates they are less effective than several other licensed non-opioid analgesics. Notably, patients may not benefit from gabapentin and pregabalin but remain at risk of adverse drug reactions. Furthermore, greater availability has resulted in increased diversion of gabapentin and pregabalin; creating problems within the opioid misuse population and prison service. As a consequence, both gabapentin and pregabalin may soon be controlled under the Misuse of Drugs Act 1971. Prescribers should be aware of the very limited clinical evidence for use of gabapentin and pregabalin outside their licensed indications, as well as their capacity to do harm.

Electrocardiographic effects of methylphenidate overdose.

OBJECTIVES: Stimulants used in the management of attention-deficit hyperactivity disorder have been associated with an increased risk of sudden cardiac death. One mechanism could involve drug-induced repolarization delay, reflected as prolongation of the QT interval on the electrocardiogram, which has been described in some recipients of methylphenidate in therapeutic doses. Because QT prolongation is usually dose-related, this study was performed to investigate effects of methylphenidate overdose on the QT interval. METHODS: Adults with methylphenidate overdose identified retrospectively were matched for sex and heart rate with a control subject with overdose of a noncardiotoxic substance, mainly acetaminophen. Notes were reviewed for clinical details and coingestants. Admission 12-lead electrocardiograms were individually calibrated and analyzed using a manual digitizer in a blinded manner by a single investigator. Mean QRS and QT intervals were calculated and differences between groups were analyzed. RESULTS: Twenty-three cases of methylphenidate overdose (median reported dose 120 mg, range 40-1,500 mg) were identified (10 males, 13 females, mean age 27.8 years). There were multiple coingestants. Level of consciousness and mean hemodynamic variables were within normal limits for all cases. Symptoms recorded in cases included anxiety (32%), dilated pupils (20%), abdominal pain (16%), vomiting (12%), palpitations (12%), and chest pain (8%). No arrhythmias were recorded. Mean heart rate was 92.4/min in methylphenidate cases and 93.8/min in the heart rate-matched controls. There were no significant differences between the groups in mean QRS (cases 86.1, controls 86.2, mean difference 0.1, 95% confidence interval = -5.1 to 5.0 ms) or mean QT intervals (cases 354, controls 355, mean difference -0.8, 95% confidence interval = -10.7 to 9.2 ms). CONCLUSIONS: Methylphenidate overdose is unlikely to have substantial effects on the QRS or QT intervals.

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.

Adverse reactions associated with acetylcysteine.

INTRODUCTION: Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. METHODS: A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. RESULTS: A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. CONCLUSION: This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and treatment of adverse reactions to acetylcysteine and identifies particular "at-risk" patient groups. Given the commonality of adverse reactions associated with acetylcysteine, it is important to ensure that any adverse event does not preclude patients from receiving maximal hepatic protection, particularly in the context of significant paracetamol ingestion. Further work on mechanisms should allow specific therapies to be developed.