The new analysis shows that between 2019 and 2021, 46,200 people lost their lives due to Death of Despair in England – the equivalent of 42 people every day.

However, in the North East of England more than twice as many people lost their lives due to Deaths of Despair compared to London.

Deaths of Despair is a collective term for deaths from alcohol, drugs and suicide, which tend to occur much more frequently in socially deprived communities.

The study, led by academics from Health Equity North (HEN), The University of Manchester and the National Institute for Health and Care Research (NIHR) Applied Research Collaboration Greater 91ֱ�� (ARC-GM) examined local authority data to identify geographical trends and risk factors that contribute to these kind of deaths.

The analysis found that northern regions and coastal areas of England are experiencing a much higher burden of mortality from these avoidable causes.

Out of the 20 local authority areas that experience the highest rates of Deaths of Despair, 16 are in the North, and all of the top 10 areas are in the North.

Conversely, none of the 20 local authorities with the lowest rates of Deaths of Despair are in the North.

The analysis also looked at associated factors that predict the risk of these kinds of deaths; living in the North was the strongest predictor. Local authorities with higher proportions of unemployment, white British ethnicity, people living alone, economic inactivity, employment in elementary occupations, and people living in urban areas had higher rates of Deaths of Despair.

The study found that:

• On average, 14.8 per 100,000 more people die from Deaths of Despair in the North compared to the rest of England
• Even after accounting for multiple social and economic factors, living in the North of England was associated with a 5.8 per 100,000 increase in Deaths of Despair rate
• More than twice as many people died from Deaths of Despair in the North East of England than they did in London (54.7 per 100,000 and 25.1 per 100,000 respectively)
• The highest rate of Deaths of Despair in England (at local authority level) is in Blackpool – almost 2.5 times the national average
• Three areas in England, all in the North, experienced more than double the average Deaths of Despair – Blackpool (83.8 in 100,000 deaths), Middlesbrough (71.6 per 100,000 deaths) and Hartlepool (70.5 per 100,000 deaths)
• Alcohol-specific deaths made up almost half of Deaths of Despair in England, accounting for 44.1% of all such deaths
• Deaths of Despair accounted for 2.9% of all deaths in England
• Deaths of Despair were highest among people aged 45-54 (55 per 100,000)
• Deaths of Despair accounted for 2 in 5 deaths in people aged 25-29 (41.1% of all deaths)
• Coastal local authorities had a significantly higher average Deaths of Despair rate than inland local authorities (41.6 per 100,000 compared to 31.5 per 100,000)

The study is believed to be the first of its kind to explore geographical patterning and contributing causes of deaths of despair in England.

The researchers are calling on government to prioritise preventative policies which address the longstanding inequalities across England, with fair funding allocation distributed according to need.

Christine Camacho, lead author and PhD Fellow NIHR ARC-GM, said: “Our study shows that some of the risk factors of deaths of despair have a more pronounced impact in the North of England, where inequalities in health and wealth are persistent and have widened during recent decades.

“As well as specific public health interventions to prevent deaths from drugs, alcohol and suicide, we need to move further and faster with Levelling Up in England to tackle the underlying inequalities which are leading people to die from despair.”

, Co-Academic Director at Health Equity North, and Senior Lecturer in Health Economics at The University of Manchester, said: “Time and time again, we see research exposing regional inequity with the North of England often being hit the hardest. Unsurprisingly, the findings of this study further highlight the persistent health inequalities in northern regions. This can’t be ignored – it is not acceptable that more than twice as many people in some deprived communities in the North are dying due to deaths of this nature.

“This research provides policymakers with a novel insight into the associated social factors of deaths of despair, which can help when developing comprehensive strategies that not only target specific risk factors but also consider the intricate relationships among these causes, contributing to more effective prevention and intervention efforts.”

Researchers from The University of Manchester have discovered a new way of manipulating key assembly line enzymes in bacteria which could pave the way for a new generation of antibiotic treatments.

New research published today in , describes how CRISPR-Cas9 gene editing can be used to create new nonribosomal peptide synthetase (NRPS) enzymes that deliver clinically important antibiotics. NRPS enzymes are prolific producers of natural antibiotics such as penicillin. However, up until now, manipulating these complex enzymes to produce new and more effective antibiotics has been a major challenge.

The antimicrobial resistance () infections are estimated to cause 700,000 deaths each year globally and are predicted to rise to 10 million, costing the global economy $100 trillion, by 2050. AMR also threatens many of the UN’s Sustainable Development Goals (SDGs), with an extra 28 million people that could be forced into extreme poverty by 2050 unless AMR is contained.

The 91ֱ�� team says the gene editing process could be used to produce improved antibiotics and possibly lead to the development of new treatments helping in the fight against drug-resistant pathogens and illnesses in the future. , Professor of Chemical Biology at the 91ֱ�� Institute of Biotechnology (), UK, explains: “The emergence of antibiotic-resistant pathogens is one of the biggest threats we face today.”

“The gene editing approach we developed is a very efficient and rapid way to engineer complex assembly line enzymes that can produce new antibiotic structures with potentially improved properties.”

Microorganisms in our environment, such as soil dwelling bacteria, have evolved nonribosomal peptide synthetase enzymes (NRPS) that assemble building blocks called amino acids into peptide products which often have very potent antibiotic activity. Many of the most therapeutically important antibiotics, used in the clinic today, are derived from these NRPS enzymes (e.g. penicillin, vancomycin and daptomycin).

Unfortunately, deadly pathogens are emerging which are resistant to all of these existing antibiotic drugs. One solution could be to create new antibiotics with improved properties that can evade the resistance mechanisms of the pathogens. However, the nonribosomal peptide antibiotics are very complex structures which are difficult and expensive to produce by normal chemical methods. To address this, the 91ֱ�� team use gene editing to engineer the NRPS enzymes, swapping domains that recognise different amino acid building blocks, leading to new assembly lines that can deliver new peptide products.

Micklefield added: “We are now able to use gene editing to introduce targeted changes to complex NRPS enzymes, enabling alternative amino acids precursors to be incorporated into the peptide structures. We are optimistic that our new approach could lead to new ways of making improved antibiotics which are urgently needed to combat emerging drug-resistant pathogens.”

The research paper is published in Nature Communications:

by; W. L. Thong, Y. Zhang, Y. Zhuo, K. J. Robins, J. K. Fyans, A. J. Herbert, B. J. C. Law & J. Micklefield* Nature Commun. 2021.

A small but significant minority of people who use illicit opioids such as heroin may unknowingly be using a powerful and potentially harmful synthetic opioid that has been linked to a number of deaths.

This is according to the results of a pilot study carried out by health and social care charity and researchers from The University of Manchester, which is published for the first time this month in the Journal of Clinical Toxicology.

The study was launched to improve understanding of the health risks facing people who use illicit opioids and the steps that could be taken to mitigate these. For the research pilot, more than 460 adults receiving treatment from Change Grow Live, one of the UK’s main providers of drug and alcohol treatment, were additionally screened for the presence of fentanyl.

While fentanyl is a very widely used and valued medication, that is legitimately prescribed for people in pain, around the world it is increasingly being sold illicitly.

The results showed a fentanyl-positive rate in adults receiving treatment for opioid use of three per cent. Of those who tested positive for the presence of fentanyl, a majority (80 per cent) was unaware of having purchased or used fentanyl.

The study was conducted at 14 Change Grow Live sites across all nine geographic regions of England. Urine screening was used to detect the presence of fentanyl, while self-report data was collected from individuals to determine whether fentanyl had been knowingly purchased and used.

The new research comes after official figures from the Office for National Statistics (ONS) released earlier this year showed an increase in deaths caused by fentanyl. The official figures showed that fatalities involving fentanyl increased by 29 per cent from 2016 to 2017, from 58 to 75 deaths.

The research builds on Change Grow Live’s work to understand the growing threat posed by fentanyl. Sparked by the charity’s direct experience of managing and learning from fentanyl-related issues in its cohort of service users in collaboration with Volteface, the independent organisation that covers the policy and politics of drugs, it convened an expert round-table last year to discuss the most effective methods of addressing the lethal threat posed by fentanyl and similar substances. The resulting action plan included recommendations for drug and alcohol treatment providers and those who commission their services based around three key areas: prevention; detection; and control.

Commenting on the research findings, Dr Prun Bijral, Medical Director at Change Grow Live and lead author of the report, said:

“As with any pilot study, the findings need to be kept in perspective and we should be cautious about drawing definitive conclusions. However, in spite of these important caveats, this research was carried out across each of England’s nine regions and we can therefore reasonably say that it does give us an indication of the possible prevalence of fentanyl, where previously there was an absence of data.

“The data suggests that fentanyl is not only present in England, but may be more widespread than originally thought. Although we are not yet seeing a problem on the scale of the USA and Canada, there is no room for complacency.

“We need to build on the work and efforts already underway across the public health landscape, from ensuring that warnings about the prevalence and dangers of fentanyl are adequately communicated and understood, to exploring all options to reduce the risks of drug-related harm including the optimisation of medication-assisted treatment to address problematic opioid use, and distributing naloxone, a drug which can save lives in the event of an overdose situation.”

Professor Tim Millar, Professor of Substance Use and Addictions at the University of Manchester, said:

“Although it is difficult to reach definitive conclusions on the basis of this preliminary pilot study, we think it is important to highlight the possibility that there may be more fentanyl in circulation than many people, us included, had thought. We’re in the process of planning a more comprehensive, larger study that will help to clarify these initial results.”