Edinburgh Clinical Toxicology

Paracetamol overdose is very common. Someone presents to the hospital following an overdose every 5 minutes across the UK. This rate is the same as the rate for heart attacks. Despite having an effective antidote called acetylcysteine (NAC), 1 in 10 patients go on to develop liver damage. NAC causes side effects such as allergic reactions that are unpleasant for the patient and may result in this essential treatment being stopped. It is unknown whether increasing the dose of NAC is more effective at preventing liver damage partly because, until recently, dose increases have not been possible due to the side effects.

To address this, we designed a new protocol for giving NAC (the SNAP regimen) that is now used across the UK and has dramatically reduced the risk of patients experiencing side effects. The improved safety of the SNAP regimen allows us to look at the potential benefits of treating patients with higher NAC doses. This trial will determine whether increasing the NAC dose results in an increase in the breakdown of paracetamol, without causing an unacceptable rate of side-effects.

Project overview

The aim of this clinical trial is to test the safety of a cell therapy for liver injury. Healthy people with no liver disease can develop sudden acute liver injury which, in severe cases, can lead to a syndrome called acute liver failure. Acute liver failure is characterised by bleeding because the liver cannot make enough clotting factors, excessive pressure in the brain, kidney failure, and infection.

Acute liver failure has no effective treatment other than liver transplantation, which has only limited use because of its associated complications, the expense to the health provider and the scarcity of donor's livers. Medicines are the most common cause of acute liver failure in the Western world, especially paracetamol when taken in overdose. The only treatment for paracetamol overdose is called acetylcysteine, which is optimally effective only if treatment is started within around 8 hours of taking the tablets. For other causes of acute liver failure, there are currently no specific treatments.

Our new treatment is an infusion of cells called macrophages, which are large white blood cells that clear away damaged liver cells, and reduce inflammation, and, in mice with acute liver failure have been shown to promote the regeneration of healthy liver tissue.

Project overview

Paracetamol overdose is common, with about 100,000 cases per year. Around 50,000 of these are treated and around 5,000 develop liver injury. The most common treatment used is called N-acetylcysteine (NAC). The sooner treatment with NAC is started after paracetamol overdose, the greater the likelihood that drug-induced liver injury will be prevented. The current biomarker (a molecule in the blood) that shows us the extent of drug-induced liver injury is called ALT, and it is a reliable gold standard for established liver injury. However, ALT increases too slowly after paracetamol overdose for the diagnosis of liver injury to occur so that treatment with NAC can have the best possible outcome.

There is a need for an assay (a quick test) capable of telling us quicker that patients are likely to develop liver injury after paracetamol overdose to improve treatment knowledge and hopefully a better outcome. K18 is another biomarker that is seen in liver injury earlier on than ALT. To try and improve patient care researchers have created a capillary blood (taken from a fingerpick), quantitative (can be measured), K18 Lateral Flow Assay/test (K18-LFA) that is low-cost, rapid and reliable. These look the same as the COVID-19 tests and can be read by the naked eye. The researchers also plan to test a device that uses a low-powered laser to read the strip and give a value (called a Raman Reader).

Project overview

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A global research and policy initiative dedicated to preventing deaths from pesticide self-poisoning.

Pesticide ingestion is one of the most common methods of suicides worldwide, responsible for an estimated 14 million deaths since the Green Revolution in the 1960s. The majority of these deaths occur in agricultural communities in low and middle-income countries where people have easy access to lethal pesticides.

The most effective way to save lives is to ban acutely toxic highly hazardous pesticides. This is an approach recommended by the United Nations, including the World Health Organization and the Food and Agriculture Organization.

The Centre for Pesticide Suicide Prevention works in countries where pesticide self-poisoning is a recognised and significant health problem. It works in partnership with national policy-makers, along with international organizations, supporting reforms to ban lethal pesticides.

Centre for Pesticide Suicide Prevention website

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A large-scale randomised controlled clinical trial in Bangladesh, exploring new treatments for patients with organophosphorus (OP) or carbonate poisoning, in partnership with the Toxicology Society of Bangladesh.

Organophosphorus and carbamate insecticides are responsible for around two thirds of pesticide poisoning deaths across the world. Current treatments do not always work and, despite thousands of studies and millions of deaths, no new treatments have been introduced in 50 years.

Previous studies have suggested that calcium channel blocking medicines [CCB] or magnesium may help to reduce the pesticides’ effects and prevent deaths. However, there is no clear information on whether these medicines work. This study hopes to determine whetehr these relatively cheap, widely available treatments can help treat patients poisoned by these anticholinesterase insecticides.

It is funded by the Joint Global Health Trials initiative, a collaboration between MRC, Wellcome Trust, DFID and NIHR. If successful, the study will result in the first new treatment for these forms of poisoning for 50 years.

Project overview on Toxicology Society of Bangladesh website

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A large-scale randomised controlled study testing whether pesticide vendor training is an effective way to reduce pesticide self-poisoning in rural Asia, in partnership with the Rajarata University of Sri Lanka and South Asian Clinical Toxicology Research Collaboration.

The project involves delivering training to shopkeepers to help them identify people at risk of drinking pesticides, so that they do not sell to them. The vendors are taught how to observe customer behaviour, check for intoxication, and ask questions which farmers should know the answer to. It follows a previous pilot study that suggested this might possibly be an effective approach.

The study is taking place over 5 years in 71 divisional secretariats within North Central, Eastern, Northern and Central Provinces of Sri Lanka. This covers a population of 2.5 million people, working with around 1,500 vendors from 1,000 pesticide shops.

It will compare the effect of training on the number of patients presenting to hospital with pesticide self-poisoning in the province. It will also look for evidence of people switching to other methods of self-harm.

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An international research programme that aims to improve diagnosis, treatment and knowledge of acute poisoning in low and middle-income countries (LMIC).

The programme aims to prevent deaths by developing new knowledge, diagnostics, treatments, informed policies and capacity. The work will directly benefit countries involved in the research, including Bangladesh, Sri Lanka, and India.

The project comprises 5 work packages focused on methanol, pesticides, guidance, research capacity, and poison information centres. It also includes an academic training programme (the Global Academy for Clinical Toxicology) to develop and train the clinical toxicology researchers of the future.

It is funded by the NIHR Research and Innovation for Global Health Transformation (RIGHT) programme. Key partners include the South Asian Clinical Toxicology Research Collaboration, Toxicology Society of Bangladesh and Postgraduate Institute of Medical Education and Research, Chandigarh.

NIHR RIGHT4: Preventing Deaths from Acute Poisoning in LMIC website

A high number of people are dying every year from combined opioid (e.g. heroin, methadone) and benzodiazepine (e.g.  diazepam, etizolam) overdoses. An effective opioid antidote, naloxone, is available and used pre-hospital to save lives. A similar antidote for benzodiazepines (flumazenil) exists but is not used due to concerns about seizures. This study will determine whether flumazenil can be safely and effectively administered by intramuscular injection which may allow it to be used pre-hospital to save lives.

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The Drugs Research Network for Scotland (DRNS) exists to support and promote collaborative drugs research across disciplines, higher education institutions, health and social care providers, criminal justice services, voluntary sector providers, local communities, people who use drugs and their families across Scotland.

DRNS aims to inform the development of Scottish policy and practice by brokering links and supporting productive relationships across organisations and sectors of society. 

Our priorities include the delivery of a range of knowledge exchange events to share emerging learning, facilitate networking, and support the translation of research evidence into social impact. We also synthesise and summarise evidence to address key information needs and to shape emerging areas of policy and practice across Scotland. 

DRNS is funded by the Scottish Government and is a cross-College initiative with the School of Health in Social Science.

Drugs Research Network for Scotland (DRNS) website