̽��ֱ�� of Cambridge - National Institute for Health Research (NIHR)

One in four patients in vegetative or minimally conscious state able to perform cognitive tasks, study finds

cjb250 — Wed, 14 Aug 2024 21:00:11 +0000

Severe brain injury can leave individuals unable to respond to commands physically, but in some cases they are still able to activate areas of the brain that would ordinarily play a role in movement. This phenomenon is known as ‘cognitive motor dissociation’.

To determine what proportion of patients in so-called ‘disorders of consciousness’ experience this phenomenon – and help inform clinical practice – researchers across Europe and North America recruited a total of 353 adults with disorders of consciousness, including the largest cohort of 100 patients studied at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust.

Participants had mostly sustained brain injury from severe trauma, strokes or interrupted oxygen supply to the brain after heart attacks. Most were living in specialised long-term care facilities and a few were living at home with extensive care packages. ̽��ֱ��median time from injury for the whole group was about eight months.

Researchers assessed patterns of brain activation among these patients using functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). Subjects were asked to repeatedly imagine performing a motor activity (for example, “keep wiggling your toes”, “swinging your arm as if playing tennis”, “walking around your house from room to room”) for periods of 15 to 30 seconds separated by equal periods of rest. To be able to follow such instructions requires not only the understanding of and response to a simple spoken command, but also more complex thought processes including paying attention and remembering the command.

̽��ֱ��results of the study are published today in the New England Journal of Medicine.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge said: “When a patient has sustained a severe brain injury, there are very important, and often difficult, decisions to be made by doctors and family members about their care. It’s vitally important that we are able to understand the extent to which their cognitive processes are still functioning by utilising all available technology.”

Among the 241 patients with a prolonged disorder of consciousness, who could not make any visible responses to bedside commands, one in four (25%) was able to perform cognitive tasks, producing the same patterns of brain activity recorded with EEG and/or fMRI that are seen in healthy subjects in response to the same instructions.

In the 112 patients who did demonstrate some motor responses to spoken commands at the bedside, 38% performed these complex cognitive tasks during fMRI or EEG. However, the majority of these patients (62%) did not demonstrate such brain activation. This counter-intuitive finding emphasises that the fMRI and EEG tasks require patients to have complex cognitive abilities such as short-term memory and sustained concentration, which are not required to the same extent for following bedside commands.

These findings are clinically very important for the assessment and management of the estimated 1,000 to 8,000 individuals in the UK in the vegetative state and 20,000 to 50,000 in a minimally conscious state. ̽��ֱ��detection of cognitive motor dissociation has been associated with more rapid recovery and better outcomes one year post injury, although the majority of such patients will remain significantly disabled, albeit with some making remarkable recoveries.

Dr Judith Allanson, Consultant in Neurorehabilitation, said: “A quarter of the patients who have been diagnosed as in a vegetative or minimally conscious state after detailed behavioural assessments by experienced clinicians, have been found to be able to imagine carrying out complex activities when specifically asked to. This sobering fact suggests that some seemingly unconscious patients may be aware and possibly capable of significant participation in rehabilitation and communication with the support of appropriate technology.

“Just knowing that a patient has this ability to respond cognitively is a game changer in terms of the degree of engagement of caregivers and family members, referrals for specialist rehabilitation and best interest discussions about the continuation of life sustaining treatments.”

̽��ֱ��researchers caution that care must be taken to ensure the findings are not misrepresented, pointing out, for example, that a negative fMRI/EEG result does not per se exclude cognitive motor dissociation as even some healthy volunteers do not show these responses.

Professor John Pickard, emeritus professorial Fellow of St Catharine's College, Cambridge, said: “Only positive results – in other words, where patients are able to perform complex cognitive processes – should be used to inform management of patients, which will require meticulous follow up involving specialist rehabilitation services.”

̽��ֱ��team is calling for a network of research platforms to be established in the UK to enable multicentre studies to examine mechanisms of recovery, develop easier methods of assessment than task-based fMRI/EEG, and to design novel interventions to enhance recovery including drugs, brain stimulation and brain-computer interfaces.

̽��ֱ��research reported here was primarily funded by the James S. McDonnell Foundation. ̽��ֱ��work in Cambridge was supported by the National Institute for Health and Care Research UK, MRC, Smith’s Charity, Evelyn Trust, CLAHRC ARC fellowship and the Stephen Erskine Fellowship (Queens’ College).

Reference
Bodien, YG et al. Cognitive Motor Dissociation in Disorders of Consciousness. NEJM; 14 Aug 2024; DOI: 10.1056/NEJMoa2400645

Adapted from a press release from Weill Cornell Medicine

Around one in four patients with severe brain injury who cannot move or speak – because they are in a prolonged coma, vegetative or minimally conscious state – is still able to perform complex mental tasks, a major international study has concluded in confirmation of much smaller previous studies.

When a patient has sustained a severe brain injury, there are very important, and often difficult, decisions to be made by doctors and family members about their care

Emmanuel Stamatakis

Witthaya Prasongsin (Getty Images)

Male patient in a hospital bed - stock image

Acknowledgements

̽��ֱ��multidisciplinary Cambridge Impaired Consciousness Research Group, led by Emeritus Professors John Pickard (Neurosurgery) & David Menon (Anaesthesia) and Drs Judith Allanson & Emmanuel A. Stamatakis (Lead, Cognition and Consciousness Imaging Group), started its research programme in 1997, partly in response to emerging concern over the misdiagnosis of the vegetative state. This pioneering work has only been possible by having access to the world class resources of the Wolfson Brain Imaging Centre, the NIHR/Wellcome Clinical Research Facility at Addenbrooke’s Hospital, the MRC Cognition and Brain Sciences Unit (Professors Barbara Wilson & Adrian Owen), the Royal Hospital for Neuro-disability (Putney) and the Central England Rehabilitation Unit (Royal Leamington Spa).

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Ultra-processed food makes up almost two-thirds of calorie intake of UK adolescents

cjb250 — Wed, 17 Jul 2024 01:30:13 +0000

̽��ֱ��study found that UPF consumption was highest among adolescents from deprived backgrounds, those of white ethnicity, and younger adolescents.

UPFs are food items that are manufactured from industrial substances and contain additives such as preservatives, sweeteners, colourings, flavourings, and emulsifiers. UPFs vary greatly, but tend to indicate poor dietary quality, with higher levels of added sugars, saturated fat, and sodium, as well as decreased fibre, protein, and micronutrient content. They have been suggested as one of the key drivers of the global rise in diseases such as obesity, type 2 diabetes, and cancer.

Globally, the availability and sales of UPFs have increased over time and previous evidence suggests that this has led to increased consumption among adolescents. To look at trends within the UK, researchers from Cambridge and Bristol analysed data from four-day food diaries of almost 3,000 adolescents in the UK National Diet and Nutrition Survey between 2008/09 and 2018/19.

In research published today in the European Journal of Nutrition, the researchers found that a mean of 66% of adolescents’ energy intake came from UPF consumption during this period, though there was a slight fall from 68% to 63% between 2008/09 and 2018/2019.

Parents’ occupation, ethnic group and UK region all influenced the proportion of calorie intake from UPFs:

Adolescents from disadvantaged backgrounds consumed a higher proportion of their calorie intake from UPFs compared to adolescents from less disadvantaged backgrounds (68.4% compared with 63.8%).
Adolescents from a non-white ethnicity consumed a lower proportion of their calorie intake from UPFs (59.0% compared with 67.3%).
Adolescents living in the North of England consumed a higher proportion of their calorie intake from UPFs compared with those living in the South of England and London (67.4% compared with 64.1%).
18-year-olds consumed a lower proportion of their calorie intake from UPFs compared with 11-year-olds (63.4% compared with 65.6%).

Dr Yanaina Chavez-Ugalde from the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, the study’s first author, said: “Adolescents’ food patterns and practices are influenced by many factors, including their home environment, the marketing they are exposed to and the influence of their friends and peers. But adolescence is also an important time in our lives where behaviours begin to become ingrained.

“It’s clear from our findings that ultra-processed foods make up the majority of adolescents’ diets, and their consumption is at a much higher level than is ideal, given their potential negative health impacts.”

̽��ֱ��researchers argue that the observed reduction in UPF intake pre-pandemic could be partly explained by an increased public awareness and health concerns associated with sugar consumption, government-led campaigns, sugar-taxes in other countries and the reformulation of sugary drinks to reduce their sugar content.

Dr Esther van Sluijs from the MRC Epidemiology Unit at Cambridge, joint senior author, said: “Ultra-processed foods offer convenient and often cheaper solutions to time- and income-poor families, but unfortunately many of these foods also offer poor nutritional value. This could be contributing to the inequalities in health we see emerging across childhood and adolescence.”

Dr Zoi Toumpakari from the Centre for Exercise, Nutrition and Health Sciences at the ̽��ֱ�� of Bristol, joint senior author, added: “Our findings suggest that disparities in consumption of ultra-processed foods are not just down to individual choices. We hope this evidence can help guide policymakers in designing more effective policies to combat the negative effects of ultra-processed food consumption among youth and the ripple effects this has on public health.”

This study was largely funded by the National Institute for Health and Care Research School for Public Health Research.

Reference
Chavez-Ugalde, Y et al. Ultra-processed food consumption in UK adolescents: distribution, trends, and sociodemographic correlates using the National Diet and Nutrition Survey 2008/09 to 2018/19. Eur J Nutr; 17 Jul 2024; DOI: 10.1007/s00394-024-03458-z

Adolescents consume around two-thirds of their daily calories from ultra-processed foods (UPFs), new research from the Universities of Cambridge and Bristol has found.

Ultra-processed foods make up the majority of adolescents’ diets, and their consumption is at a much higher level than is ideal, given their potential negative health impacts

Yanaina Chavez-Ugalde

Juanmonino (Getty Images)

Boy eating a burger

Yes

‘Wraparound’ implants represent new approach to treating spinal cord injuries

sc604 — Wed, 08 May 2024 18:01:25 +0000

A team of engineers, neuroscientists and surgeons from the ̽��ֱ�� of Cambridge developed the devices and used them to record the nerve signals going back and forth between the brain and the spinal cord. Unlike current approaches, the Cambridge devices can record 360-degree information, giving a complete picture of spinal cord activity.

Tests in live animal and human cadaver models showed the devices could also stimulate limb movement and bypass complete spinal cord injuries where communication between the brain and spinal cord had been completely interrupted.

Most current approaches to treating spinal injuries involve both piercing the spinal cord with electrodes and placing implants in the brain, which are both high-risk surgeries. ̽��ֱ��Cambridge-developed devices could lead to treatments for spinal injuries without the need for brain surgery, which would be far safer for patients.

While such treatments are still at least several years away, the researchers say the devices could be useful in the near-term for monitoring spinal cord activity during surgery. Better understanding of the spinal cord, which is difficult to study, could lead to improved treatments for a range of conditions, including chronic pain, inflammation and hypertension. ̽��ֱ��results are reported in the journal Science Advances.

“ ̽��ֱ��spinal cord is like a highway, carrying information in the form of nerve impulses to and from the brain,” said Professor George Malliaras from the Department of Engineering, who co-led the research. “Damage to the spinal cord causes that traffic to be interrupted, resulting in profound disability, including irreversible loss of sensory and motor functions.”

̽��ֱ��ability to monitor signals going to and from the spinal cord could dramatically aid in the development of treatments for spinal injuries, and could also be useful in the nearer term for better monitoring of the spinal cord during surgery.

“Most technologies for monitoring or stimulating the spinal cord only interact with motor neurons along the back, or dorsal, part of the spinal cord,” said Dr Damiano Barone from the Department of Clinical Neurosciences, who co-led the research. “These approaches can only reach between 20 and 30 percent of the spine, so you’re getting an incomplete picture.”

By taking their inspiration from microelectronics, the researchers developed a way to gain information from the whole spine, by wrapping very thin, high-resolution implants around the spinal cord’s circumference. This is the first time that safe 360-degree recording of the spinal cord has been possible – earlier approaches for 360-degree monitoring use electrodes that pierce the spine, which can cause spinal injury.

̽��ֱ��Cambridge-developed biocompatible devices – just a few millionths of a metre thick – are made using advanced photolithography and thin film deposition techniques, and require minimal power to function.

̽��ֱ��devices intercept the signals travelling on the axons, or nerve fibres, of the spinal cord, allowing the signals to be recorded. ̽��ֱ��thinness of the devices means they can record the signals without causing any damage to the nerves, since they do not penetrate the spinal cord itself.

“It was a difficult process, because we haven’t made spinal implants in this way before, and it wasn’t clear that we could safely and successfully place them around the spine,” said Malliaras. “But because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important area.”

̽��ֱ��devices were implanted using an adaptation to routine surgical procedure so they could be slid under the spinal cord without damaging it. In tests using rat models, the researchers successfully used the devices to stimulate limb movement. ̽��ֱ��devices showed very low latency – that is, their reaction time was close to human reflexive movement. Further tests in human cadaver models showed that the devices can be successfully placed in humans.

̽��ֱ��researchers say their approach could change how spinal injuries are treated in future. Current attempts to treat spinal injuries involve both brain and spinal implants, but the Cambridge researchers say the brain implants may not be necessary.

“If someone has a spinal injury, their brain is fine, but it’s the connection that’s been interrupted,” said Barone. “As a surgeon, you want to go where the problem is, so adding brain surgery on top of spinal surgery just increases the risk to the patient. We can collect all the information we need from the spinal cord in a far less invasive way, so this would be a much safer approach for treating spinal injuries.”

While a treatment for spinal injuries is still years away, in the nearer term, the devices could be useful for researchers and surgeons to learn more about this vital, but understudied, part of human anatomy in a non-invasive way. ̽��ֱ��Cambridge researchers are currently planning to use the devices to monitor nerve activity in the spinal cord during surgery.

“It’s been almost impossible to study the whole of the spinal cord directly in a human, because it’s so delicate and complex,” said Barone. “Monitoring during surgery will help us to understand the spinal cord better without damaging it, which in turn will help us develop better therapies for conditions like chronic pain, hypertension or inflammation. This approach shows enormous potential for helping patients.”

̽��ֱ��research was supported in part by the Royal College of Surgeons, the Academy of Medical Sciences, Health Education England, the National Institute for Health Research, MRC Confidence in Concept, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

Reference:
Ben J Woodington, Jiang Lei et al. ‘Flexible Circumferential Bioelectronics to Enable 360-degree Recording and Stimulation of the Spinal Cord.’ Science Advances (2024). DOI: 10.1126/sciadv.adl1230

A tiny, flexible electronic device that wraps around the spinal cord could represent a new approach to the treatment of spinal injuries, which can cause profound disability and paralysis.

Because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important area

George Malliaras

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY

Illustration of spinal cord

Yes

Report highlights inequalities and hidden suffering among people living with breast cancer

cjb250 — Mon, 15 Apr 2024 22:31:36 +0000

Many people with breast cancer ‘systematically left behind’, say researchers in Lancet Commission led by Professor Charlotte Coles.

UK ‘sugar tax’ linked to fall in child hospital admissions for tooth extraction

Anonymous — Wed, 15 Nov 2023 00:00:45 +0000

In a study published today in BMJ Nutrition, Prevention & Health, researchers at the Medical Research Council (MRC) Epidemiology Unit at Cambridge found that the levy may have reduced the number of under-18s having a tooth removed due to tooth decay by 12%. ̽��ֱ��largest reductions were in children aged up to nine years old.

Sugar-sweetened drinks account for around 30% of the added sugars in the diets of children aged one to three years and over a half by late adolescence. In England, nearly 90% of all tooth extractions in young children are due to decay, resulting in around 60,000 missed school days a year.

̽��ֱ��World Health Organization has recommended a tax on sugar-sweetened drinks to reduce sugar consumption, which more than 50 countries have implemented. In March 2016, the UK Government announced a soft drinks industry levy or ‘sugar tax’, which aimed to reduce sugar intake by encouraging drinks manufacturers to reformulate their products. ̽��ֱ��levy was implemented in April 2018.

While the relationship between sugar-sweetened drinks and tooth decay is well established, no studies have used real-world data to examine the relationship between the levy and dental health.

To address this, the researchers analysed hospital admissions data for tooth extractions due to tooth decay in children up to 18 years old in England from January 2014 to February 2020. They studied trends overall as well as broken down by neighbourhood deprivation and age groups.

Overall, in children aged 18 and under, there was an absolute reduction in hospital admissions of 3.7 per 100,000 population per month compared to if the soft drinks levy had not happened. This equated to a relative reduction of 12% compared to if the levy had not been introduced.

Based on a population of nearly 13 million children in England in 2020, the researchers estimated that the reduction avoided 5,638 admissions for tooth decay. Reductions in hospital admissions were greatest in younger children aged up to four years and among children aged five to nine years, with absolute reductions of 6.5 and 3.3 per 100,000 respectively.

Dr Nina Rogers from the MRC Epidemiology Unit at the ̽��ֱ�� of Cambridge, the study’s first author, said: “This is an important finding given that children aged five to nine are the most likely to be admitted to hospital for tooth extractions under general anaesthesia.”

No significant changes in admission rates for tooth decay were seen in older age groups of 10–14 years and 15–18 years. However, reductions in hospital admissions were seen in children living in most areas regardless of deprivation.

As this is an observational study and because there was no comparable control group, the researchers cannot say definitively that the soft drinks levy caused this reduction in tooth decay. They acknowledge that other national interventions such as the sugar reduction programme and compulsory nutrition labels alongside the levy may have raised public awareness of sugar consumption and influenced buying habits.

Nevertheless, they conclude that their study “provides evidence of possible benefits to children’s health from the UK soft drinks industry levy beyond obesity which it was initially developed to address.”

Professor David Conway, co-author, and professor of dental public health at ̽��ֱ�� of Glasgow added: “Tooth extractions under general anaesthesia is among the most common reason for children to be admitted to hospital across the UK. This study shows that ambitious public health policies such as a tax on sugary drinks can impact on improving child oral health.”

̽��ֱ��research was funded by the Medical Research Council and the National Institute for Health and Care Research.

Reference
Rogers, N T et al. Estimated impact of the UK soft drinks industry levy on childhood hospital admissions for carious tooth extractions: interrupted time series analysis. BMJ Nutrition Prevention & Health; 14 Nov 2023; DOI:10.1136/bmjnph-2023-000714

Adapted from a press release from the BMJ.

̽��ֱ��UK soft drinks industry levy introduced in 2018 may have saved more than 5,500 hospital admissions for tooth extractions, according to an analysis by researchers at the ̽��ֱ�� of Cambridge.

This is an important finding given that children aged five to nine are the most likely to be admitted to hospital for tooth extractions under general anaesthesia

Nina Rogers

Michal Jarmoluk (Pixabay)

Child receiving dental treatment

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Licence type:

Public Domain

Risk of premature birth from smoking while pregnant more than double previous estimates

cjb250 — Wed, 27 Sep 2023 23:01:31 +0000

̽��ֱ��study, published today in the International Journal of Epidemiology, also found that smoking meant that the baby was four times more likely to be small for its gestational age, putting it at risk of potentially serious complications including breathing difficulties and infections.

But the team found no evidence that caffeine intake was linked to adverse outcomes.

Women are currently recommended to stop smoking and limit their caffeine intake during pregnancy because of the risk of complications to the baby. For example, smoking during pregnancy is associated with an increased risk of fetal growth restriction, premature birth and low birthweight, though it has also been linked to a reduced risk of preeclampsia (high blood pressure during pregnancy).

High caffeine intake has also been shown to be associated with lower birthweights and possibly fetal growth restriction. Caffeine is more difficult to avoid than cigarette smoke as is found in coffee, tea, chocolate, energy drinks, soft drinks, and certain medications.

Studies looking at the links between smoking, caffeine and adverse pregnancy outcomes tend to rely on self-reported data to estimate exposure, which is not always reliable. A more objective measure is to look at levels of metabolites in the blood – chemical by-products created when substances such as tobacco and caffeine are processed in the body.

Researchers at the ̽��ֱ�� of Cambridge and the Rosie Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, recruited more than 4,200 women who attended the hospital between 2008 and 2012 as part of the Pregnancy Outcome Prediction (POP) study. ̽��ֱ��team analysed blood samples taken from a subset of these women four times during their pregnancies.

To assess exposure to cigarette smoke, the team looked at levels of the metabolite cotinine, which can be detected in blood, urine, and saliva. Only two out of three women with detectable levels of cotinine in every blood sample were self-reported smokers, showing that this measure is a more objective way of assessing smoking behaviour.

A total of 914 women were included in the smoking analysis. Of these, 78.6% were classified as having no exposure to smoking while pregnant, 11.7% as having some exposure and 9.7% as having consistent exposure.

Compared to women who were not exposed to smoking while pregnant, those with consistent exposure were 2.6 times more likely to experience spontaneous preterm birth – more than double the previous estimate of 1.27 from a meta-analysis of studies – and 4.1 times as likely to experience fetal growth restriction.

Babies born to smokers were found to be on average 387g lighter than babies born to non-smokers – that is, more than 10% smaller than the weight of an average newborn. This increases the risk that the baby will have a low birth weight (2.5kg or less), which in turn is linked to an increased risk of developmental problems as well as poorer health in later life.

Unlike in previous studies, however, the team found no evidence that smoking reduced the risk of pre-eclampsia.

Professor Gordon Smith, Head of the Department of Obstetrics and Gynaecology at the ̽��ֱ�� of Cambridge, said: “We’ve known for a long time that smoking during pregnancy is not good for the baby, but our study shows that it’s potentially much worse than previously thought. It puts the baby at risk of potentially serious complications from growing too slowly in the womb or from being born too soon.

“We hope this knowledge will help encourage pregnant mums and women planning pregnancy to access smoking-cessation services. Pregnancy is a key time when women quit and if they can remain tobacco free after the birth there are lifelong benefits for them and their child.”

Smoking cessation is offered routinely to all pregnant women and the NHS has local smoking cessation services for anyone, pregnant or not. Further information is available on the NHS website.

To assess caffeine intake, they researchers looked for the metabolite paraxanthine, which accounts for 80% of caffeine metabolism and is both less sensitive to recent intake and more stable throughout the day.

915 women were included in the caffeine analysis. Of these women, 12.8% had low levels of paraxanthine throughout pregnancy (suggesting low caffeine intake), 74.0% had moderate levels and 13.2% had high levels. There was little evidence of an association between caffeine intake and any of the adverse outcomes.

̽��ֱ��work was supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre and the Medical Research Council.

Reference
Selvaratnam, RJ et al. Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcome. International Journal of Epidemiology; 28 Sept 2023; DOI: 10.1093/ije/dyad123

Cambridge researchers have found that women who smoke during pregnancy are 2.6 times more likely to give birth prematurely compared to non-smokers – more than double the previous estimate.

We’ve known for a long time that smoking during pregnancy is not good for the baby, but our study shows that it’s potentially much worse than previously thought

Gordon Smith

Malte Mueller (Getty Images)

Pregnant woman smoking cigarette - stock illustration

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Widely-used COVID-19 antiviral could be helping SARS-CoV-2 to evolve

cjb250 — Mon, 25 Sep 2023 15:00:41 +0000

̽��ֱ��drug works by disrupting the virus’s genome, causing it to develop random mutations as it replicates, weakening the virus to prevent replication, thereby enabling clearance of infection.

But in research published today in Nature, scientists have shown that in some cases, mutated forms of the virus have been able to be transmitted from patients treated with molnupiravir and spread within the community.

Dr Christopher Ruis from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “Molnupiravir is one of a number of drugs being used to fight COVID-19. It belongs to a class of drugs that can cause the virus to mutate so much that it is fatally weakened. But what we’ve found is that in some patients, this process doesn’t kill all the viruses, and some mutated viruses can spread. This is important to take into account when assessing the overall benefits and risks of molnupiravir and similar drugs.”

Molnupiravir, marketed under the brand name Lagevrio, is licensed for the treatment of COVID-19 in several countries, including the UK, USA and Japan. It has been used to treat the disease since late 2021.

In the body, molnupiravir is converted into a molecule that disrupts the genome of the SARS-CoV-2 virus, introducing some nucleotide mutations in its RNA – randomly changing some Cs to Ts and some Gs to As. These changes mean that as the virus replicates, its progeny get weaker, reducing how quickly the virus is able to replicate and ridding the body of the virus.

However, concern has been expressed that in some cases, a number of mutated viruses may not be killed off quickly enough and so are able to infect other individuals, potentially allowing new mutated viruses to spread.

During the COVID-19 pandemic, a number of countries – spearheaded by the Cambridge-led COVID-19 Genomics UK Consortium – sequenced virus samples, depositing the information in databases such as the Global Initiative on Sharing All Influenza Data (GISAID) and the International Nucleotide Sequence Database Collaboration (INSDC). This allowed scientists and public health agencies to track the evolution and spread of the virus, and in particular to look out for so-called ‘variants of concern’ – versions of the virus with mutations that might make them more transmissible, more lethal, or able to evade the immune system of vaccinated individuals, such as the Delta and Omicron variants.

A team of researchers from the UK and South Africa noticed a number of viral genomes that contained a large number of mutations, particularly where Cs had changed to Ts and Gs to As. While C-to-T mutations are relatively common overall in SARS-CoV-2 evolution, G-to-A mutations occur much less frequently, and a higher proportion of G-to-A mutations is associated with molnupiravir treatment.

̽��ֱ��team then analysed a family tree of more than 15 million SARS-CoV-2 sequences in the GISAID and INSDC databases looking for which mutations had occurred at each point in the virus’s evolutionary history. They found that viruses with this signature of mutations had begun to emerge almost exclusively from 2022 onwards and in countries and age groups where molnupiravir was being widely used to treat COVID-19.

To confirm the link, the researchers examined treatment records in England and found that at least one in three of viruses showing the mutational signature involved the use of molnupiravir.

̽��ֱ��researchers also saw small clusters of patients infected with mutated viruses, which suggests that these new viruses were being passed from one person to another. However, none of the known variants of concern has so far been linked to the use of molnupiravir.

Dr Theo Sanderson from the Francis Crick Institute, said: “COVID-19 is still having a major effect on human health, and some people have difficulty clearing the virus, so it’s important we develop drugs which aim to cut short the length of infection. But our evidence shows that a specific antiviral drug, molnupiravir, also results in new mutations, increasing the genetic diversity in the surviving viral population.

“Our findings are useful for ongoing assessment of the risks and benefits of molnupiravir treatment. ̽��ֱ��possibility of persistent antiviral-induced mutations needs to be taken into account for the development of new drugs which work in a similar way.”

̽��ֱ��research was funded by Wellcome, Cancer Research UK, the Medical Research Council, National Institute for Health and Care Research, Fondation Botnar, UK Cystic Fibrosis Trust and the Oxford Martin School.

Reference
Sanderson, T et al. A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes. Nature; 25 Sept 2023: DOI: 10.1038/s41586-023-06649-6

Molnupiravir, an antiviral drug used to treat patients with COVID-19, appears to be driving SARS-CoV-2 to mutate and evolve, with some of these new viruses being transmitted onwards, a new study has shown. It is not clear, however, whether these mutated viruses pose an increased risk to patients or are able to evade the vaccine.

Molnupiravir belongs to a class of drugs that can cause the virus to mutate so much that it is fatally weakened. But what we’ve found is that in some patients, this process doesn’t kill all the viruses

Christopher Ruis

visuals3Dde

SARS-CoV-2 viruses

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Licence type:

Public Domain

Radiotherapy boost cuts breast cancer treatment time by at least one week

cjb250 — Mon, 03 Jul 2023 08:04:03 +0000

Results from the IMPORT HIGH trial, published in ̽��ֱ��Lancet, show that giving some breast cancer patients a targeted additional dose of radiotherapy at the same time as treatment to the whole breast (known as simultaneous integrated boost or SIB) cuts the time taken to complete treatment by at least one week.

̽��ֱ��trial, funded by Cancer Research UK and the National Institute of Health Research and Care Research (NIHR), found that SIB radiotherapy given at the right dose works just as well as existing radiotherapy techniques in reducing the risk of the cancer returning in the treated breast.

̽��ֱ��chance of the cancer returning to the treated breast remained very low after 5 years across all treatment groups. Patients given the lower dose of SIB radiotherapy reported similar rates of side-effects, like breast hardening or firmness, as those who received the standard sequential radiotherapy schedule.

Currently, women with a higher than average risk of cancer coming back in their treated breast are given an additional radiotherapy dose to the original site of the tumour after radiotherapy is given to the entire breast. This approach, known as sequential boost, maximises the chances that any remaining cancer cells are removed from the breast.

But it takes longer for women to complete sequential boost radiotherapy, requiring them to attend more hospital appointments. In the UK, many women requiring breast boost radiotherapy are given 4 weeks of radiotherapy – 3 weeks to the whole breast with 1 week boost afterwards. In some countries, women are given 6.5 weeks of radiotherapy – 5 weeks of whole breast radiotherapy with 1-1.5 weeks boost afterwards. SIB radiotherapy cuts this down to just 3 weeks in total.

A boost treatment also increases the chance of having potentially long term side-effects after treatment, including changes in shape, size and texture of the breast that can affect women’s self-esteem and wellbeing.

In total, 2,617 patients at 76 centres took part in the trial. Patients were divided into three groups. ̽��ֱ��first group received whole breast radiotherapy with a sequential boost over 4.5 weeks in total. ̽��ֱ��second and third groups each received two different doses of SIB radiotherapy. Patients received whole breast radiotherapy with a simultaneous boost of either lower or higher dose a dose over 3 weeks in total. There was no advantage shown for those who received the higher boost dose it also led to slightly increased rates of side effects.

Professor of Breast Cancer Clinical Oncology at Cambridge ̽��ֱ��, NIHR Professor and chief investigator for the trial, Professor Charlotte Coles, said: “Some women have to live with permanent breast changes after radiotherapy which may affect their well-being. With SIB, we can deliver high-quality effective radiotherapy whilst minimising toxicity from it.

“This is a careful step towards even shorter courses of radiotherapy that include more complex techniques. By delivering more targeted boost radiotherapy over shorter time periods, women can get on with their lives more quickly."

̽��ֱ��NIHR-funded FAST Forward trial, which was also led by the ICR-CTSU and reported results in 2020, showed that whole breast radiotherapy could be given over a week. Researchers are now hoping to run another clinical trial to find out if SIB radiotherapy can be delivered to patients requiring a boost in just one week.

Professor Judith Bliss, Professor of Clinical Trials at ̽��ֱ��Institute of Cancer Research, London, Director of the Cancer Research UK-funded Clinical Trials and Statistics Unit at the ICR which is managing the IMPORT HIGH trial, said: “For some patients who have a higher risk of seeing their cancer return in the treated breast, delivering an extra, targeted boost of radiotherapy to breast tissue close to the original tumour site is an effective way to lower that risk and help keep cancer from returning to the breast.

"IMPORT HIGH has uncovered how we can streamline our delivery of these radiotherapy boosts - giving them simultaneously with whole breast radiotherapy - without impacting the effectiveness of treatment, or causing patients additional side effects. We hope this trial will change clinical practice - allowing women to benefit from sophisticated radiotherapy delivery with shorter treatment times and fewer hospital visits."

̽��ֱ��team hope that SIB radiotherapy could reduce the costs for patients travelling to hospital and cut the time taken to undergo treatment and recovery. It could be quickly adopted by the NHS and health systems worldwide as standard radiotherapy equipment is used, freeing up valuable appointment visits that could be used to treat more cancer patients sooner.

Chief Executive of Cancer Research UK, Michelle Mitchell, said: “At a time when health services across the UK are facing chronic staff shortages in cancer services, we need to look at new ways to get more patients treated as quickly as possible. In addition to training up more staff, more precise forms of radiotherapy can help to reduce the number of people who are waiting too long to begin vital treatment.

“Trials like IMPORT HIGH are leading the way in delivering smarter radiotherapy with existing technology. We hope that treatment centres across the UK and globally will rapidly adopt this approach to beat breast cancer sooner and give patients more precious time with their loved ones.”

Reference
Coles, CE et al. Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial. Lancet; 8 June 2023; DOI: 10.1016/S0140-6736(23)00619-0

Adapted from a press release by Cancer Research UK.

Treatment times for radiotherapy could be reduced for some early breast cancer patients, according to a trial led by ̽��ֱ�� of Cambridge and ̽��ֱ��Institute of Cancer Research, London.

This is a careful step towards even shorter courses of radiotherapy that include more complex techniques. By delivering more targeted boost radiotherapy over shorter time periods, women can get on with their lives more quickly

Charlotte Coles

Patrick Harrison/Cancer Research UK

Professor Charlotte Coles

Helen Lee (46) from Mepal near Cambridge

In October 2013, Helen Lee first noticed an unusual twinge in her right breast and had a hunch that something wasn’t right. Her GP couldn’t feel anything when she examined Helen but referred her to the Breast Unit at Addenbrooke’s Hospital for a mammogram to reassure her.

But, at the young age of 36, Helen was diagnosed with breast cancer. ̽��ֱ��mammogram revealed a tumour just over 2cm in size located deep in her breast tissue. She remembered:

“I felt quite relieved because I knew there was something wrong. And my surgeon said it was so deep I wouldn't have felt it. So I was actually really lucky otherwise I would have come in at 51 for screening and it might not have been treatable by then.”

Helen had surgery a few weeks after her diagnosis, followed by a course of chemotherapy. When she was due to begin radiotherapy treatment she was asked if she would like to take part in the IMPORT HIGH trial. Helen was assigned to a group receiving a targeted radiotherapy boost delivered simultaneously during her whole breast radiotherapy treatment, which reduced her treatment from 23 sessions over 4.5 weeks to 15 sessions over 3 weeks.

After undergoing surgery, chemotherapy and radiotherapy treatment, Helen has now been clear of cancer for nearly 10 years. Since her diagnosis and treatment, she has taken part regularly in Cancer Research UK Race for Life, Pretty Muddy and Shine Night Walk events in Cambridge, Bedford and Stamford, fundraising for life-saving research into future treatments for cancer patients.

Reflecting on her cancer journey, Helen said: “One thing that really struck me, at one of the first Cambridge Race for Life events that I did after my diagnosis, was watching the screen on Parker's Piece where they're playing the films where the scientists are talking about what they've been working on.

“I felt so overwhelmed that all of the people there that day were part of saving my life, and that all the people who took part in trials 10 years ago, 15 years ago, 20 years ago, everything they've done meant that I survived my cancer.”

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