Monday, January 15, 2024

Physicists identify overlooked uncertainty in real-world experiments

SANTA FE INSTITUTE

The equations that describe physical systems often assume that measurable features of the system — temperature or chemical potential, for example — can be known exactly. But the real world is messier than that, and uncertainty is unavoidable. Temperatures fluctuate, instruments malfunction, the environment interferes, and systems evolve over time.

The rules of statistical physics address the uncertainty about the state of a system that arises when that system interacts with its environment. But they’ve long missed another kind, say SFI Professor David Wolpert and Jan Korbel, a postdoctoral researcher at the Complexity Science Hub in Vienna, Austria. In a new paper published in Physical Review Research, the pair of physicists argue that uncertainty in the thermodynamic parameters themselves — built into equations that govern the energetic behavior of the system — may also influence the outcome of an experiment.

“At present, almost nothing is known about the thermodynamic consequences of this type of uncertainty despite its unavoidability,” says Wolpert. In the new paper, he and Korbel consider ways to modify the equations of stochastic thermodynamics to accommodate it.

When Korbel and Wolpert met at a 2019 workshop on information and thermodynamics, they began talking about this second kind of uncertainty in the context of non-equilibrium systems.

“We wondered, what happens if you don’t know the thermodynamic parameters governing your system exactly?” recalls Korbel. “And then we started playing around.” The equations that describe thermodynamic systems often include precisely defined terms for things like temperature and chemical potentials. “But as an experimenter or an observer you don’t necessarily know these values” to very large precision, says Korbel.

Even more vexing, they realized that it’s impossible to measure parameters like temperature, pressure, or volume precisely, both because of the limitations of measurement and the fact that these quantities change quickly. They recognized that uncertainty about those parameters not only influences information about the original state of the system, but also how it evolves.

It’s almost paradoxical, Korbel says. “In thermodynamics, you’re assuming uncertainty about your state so you describe it in a probabilistic way. And if you have quantum thermodynamics, you do this with quantum uncertainty,” he says. “But on the other hand, you’re assuming that all the parameters are known with exact precision.”

Korbel says the new work has implications for a range of natural and engineered systems. If a cell needs to sense the temperature to carry out some chemical reaction, for example, then it will be limited in its precision. The uncertainty in the temperature measurement could mean that the cell does more work — and uses more energy. “The cell has to pay this extra cost for not knowing the system,” he says.

Optical tweezers offer another example. These are high-energy laser beams configured to create a kind of trap for charged particles. Physicists use the term “stiffness” to describe the particle’s tendency to resist being moved by the trap. To determine the optimal configuration for the lasers they measure the stiffness as precisely as possible. They typically do this by taking repeated measurements, assuming that the uncertainty arises from the measurement itself.

But Korbel and Wolpert offer another possibility — that the uncertainty arises from the fact that the stiffness itself may be changing as the system evolves. If that’s the case, then repeated identical measurements won’t capture it, and finding the optimal configuration will remain elusive. “If you keep doing the same protocol, then the particle doesn’t end up in the same point, you may have to do a little push,” which means extra work that’s not described by the conventional equations.

This uncertainty could play out at all scales, Korbel says. What’s often interpreted as uncertainty in measurement may be uncertainty in the parameters in disguise. Maybe an experiment was done near a window where the sun was shining, and then repeated when it was cloudy. Or perhaps the air conditioner kicked on between multiple trials. In many situations, he says, “it’s relevant to look at this other type of uncertainty.”

JOURNAL

Physical Review Research

DOI

10.1103/PhysRevResearch.6.013021

ARTICLE TITLE

Nonequilibrium thermodynamics of uncertain stochastic processes

ARTICLE PUBLICATION DATE

8-Jan-2024

Disclaimer: AAAS

Erectile dysfunction medications may increase risk of death when combined with common chest pain medication

Medications are contraindicated but often prescribed together

Peer-Reviewed Publication

AMERICAN COLLEGE OF CARDIOLOGY

Phosphodiesterase type 5 inhibitors (PDE5i)—an erectile dysfunction drug sold under the names Viagra, Levitra, Cialis, and others—are a common medical treatment for erectile dysfunction (ED) in men with cardiovascular disease (CVD). However, a new Swedish study published today in the Journal of the American College of Cardiology suggests that patients are at higher risk for morbidity and mortality over time when PDE5is and nitrate medication are both prescribed.

Erectile dysfunction is a common condition in middle-aged and older men and is a strong predictor of coronary artery disease. Nitrates are medications commonly used to treat angina, or chest pain. Both can cause drops in blood pressure, so they are contraindicated for use together. However, there is little real-world data on the implications of using both and the number of people who are prescribed both is growing.

Serving as an update to previous studies using the same Swedish national dataset from the Swedish Patient Register, this research analyzes the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease (CAD) who are being treated with nitrates. It aims to resolve the conflicting results regarding the impact of PDE5i treatment on cardiovascular morbidity and mortality.

“Physicians are seeing an increase of requests for erectile dysfunction drugs from men with cardiovascular diseases,” said Daniel Peter Andersson, MD, PhD, Associate Professor at Karolinska Institutet in Stockholm and senior author of the study. “While there is a positive association of ED medication for men with CVD, patients taking nitrates may experience an increased risk of negative health outcomes.”

The study included 61,487 men with a history of myocardial infarction (MI) or percutaneous coronary intervention (PCI) who had received two nitrate prescriptions within six months. Exposure was defined as having received at least two filled prescriptions of any PDE5i medications. Among these men, 55,777 men were treated with nitrates and 5,710 were treated with both nitrates and PDE5i. Median follow-up time for the entire cohort was 5.7 years in nitrate only users and 3.4 years in nitrate users with PDE5i treatment. The nitrate plus PDE5i group was younger at 61.2 years compared to 70.3 years in the nitrate only users.

The researchers conducted multivariable Cox proportional hazard regression to estimate the hazard ratios (HR) with 95% confidence intervals (CI) for various health outcomes, including all-cause mortality, cardiovascular and non-cardiovascular mortality, myocardial infarction (MI), heart failure, cardiac revascularization and major cardiovascular events (MACE).

The results of the study indicate that the combined use of PDE5i treatment with nitrates is associated with a higher risk for all health outcomes compared to those taking nitrates alone. In those taking both PDE5i and nitrates, few events occurred 28 days after dispensing the PDE5is, with lower incidence rates than in subjects taking nitrates, indicating that there is low immediate risk for an event.

“Our goal is to underscore the need for careful patient-centered consideration before prescribing PDE5i medication to men receiving nitrate treatment,” Andersson said. “Furthermore, it justifies our efforts for continued research into the ambiguous effects of ED drugs on men with CVD.”

Limitations of the study include the inability to know a patient’s compliance and medication habits and the inability to infer causality of death from the data. Researchers assessed usage by filled prescriptions but did not know how compliant patients were or what their medication habits were. Also, the patient population included high-risk individuals who already had experienced MI or revascularization. They were also prescribed nitrates at least twice and despite guideline recommendations also prescribed PDE5i at least twice; thus, results may not be entirely generalizable to the general population. Further investigation is needed to fully understand the effects of the combination of treatments.

In an accompanying editorial comment, Glenn N. Levine, MD, Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, said in patients with ischemic heart disease and only mild angina with reasonable exercise ability, ED PDE5i are reasonably safe – if the patient is not on chronic nitrate therapy. However, in those on chronic oral nitrate therapy, use of PDE5i is ill-advised at best and generally contraindicated.

“ED and CAD are unfortunate, and all too common, bedfellows,” Levine said. “But, as with most relationships, assuming proper precautions and care, they can co-exist together for many years perhaps even a lifetime.”

The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at www.ACC.org or follow @ACCinTouch.

The ACC’s family of JACC Journals rank among the top cardiovascular journals in the world for scientific impact. The flagship journal, the Journal of the American College of Cardiology (JACC) — and family of specialty journals consisting of JACC: Advances, JACC: Asia, JACC: Basic to Translational Science, JACC: CardioOncology, JACC: Cardiovascular Imaging, JACC: Cardiovascular Interventions, JACC: Case Reports, JACC: Clinical Electrophysiology and JACC: Heart Failure — pride themselves on publishing the top peer-reviewed research on all aspects of cardiovascular disease. Learn more at JACC.org.

###

JOURNAL

Journal of the American College of Cardiology

ARTICLE PUBLICATION DATE

15-Jan-2024

Chronic inflammation and poverty are a ‘double whammy’ for mortality risk

Peer-Reviewed Publication

UNIVERSITY OF FLORIDA

A new study led by a University of Florida College of Public Health and Health Professions researcher finds that people with chronic inflammation living in poverty have more than double the risk of dying from heart disease and nearly triple the risk of dying from cancer within the next 15 years. The findings are based on data representing 95 million Americans ages 40 and over.

While chronic inflammation and poverty are each known to increase mortality risk, when combined, the two factors appear to have a synergistic effect, producing a greater increase in risk than if the individual effects of the two factors were merely added together, the study authors say. Their findings appear in the journal Frontiers in Medicine.

“There is a lot of existing evidence that chronic inflammation can lead to disease,” said lead author Arch Mainous III, Ph.D., a professor in the department of health services research, management and policy in the UF College of Public Health and Health Professions. “We became interested in the potential interplay of chronic inflammation with poverty, which tends to increase inflammation in its own right through factors such as chronic stress. We found that poverty and high levels of inflammation act synergistically, giving people with both factors basically a double whammy. It makes them far more likely to die and in a relatively short period of time, just 15 years.”

Acute inflammation is part of the body’s healthy short-term immune response to fighting infection, toxins or other foreign substances that may enter the body. Chronic inflammation, however, lasts for months or years and has been shown to increase the risk for developing conditions such as cancer, heart disease, Type 2 diabetes and kidney disease. Another new study led by Mainous indicates that 34.6% of U.S. adults have systemic inflammation.

Chronic inflammation can be caused by a host of lifestyle, physiological and environmental factors, such as poor diet, stress, lack of physical activity, smoking, aging, obesity, autoimmune disorders and exposure to toxins in the environment.

The findings from the UF study highlight the need for routine chronic inflammation screenings in vulnerable populations to limit what are, in many cases, preventable deaths, said Mainous, also the vice chair for research in the UF College of Medicine’s department of community health and family medicine. Currently, there are no clinical guidelines for chronic inflammation screening.

“Investigators have been studying chronic inflammation for 25 years and we have a lot of data on its role in the disease pathway and mortality,” Mainous said. “We know it’s a problem, but we don’t do anything about it. We need to translate the basic science on chronic inflammation to the doctor’s office through the creation of screening guidelines so physicians can identify chronic inflammation in their patients and work to treat the underlying causes.”

For the UF study, researchers evaluated data from the National Health and Nutrition

Examination Survey, a nationally representative survey conducted by the National Center for Health Statistics that combines survey questions with laboratory testing. The team analyzed data collected from adults ages 40 and older whose household income fell below the U.S. poverty line and whose lab tests showed elevated levels of C-reactive protein, an indicator of chronic inflammation. Records were linked to the National Death Index to track mortality over a 15-year period.

Those individuals living with both chronic inflammation and poverty had a 127% increased risk for dying from heart disease and a 196% increased risk for dying from cancer. People living with chronic inflammation or poverty, but not both factors, had about a 50% increase in mortality risk over the same period.

“It is time to move beyond documenting the health problems that inflammation can cause to trying to fix these problems,” Mainous said.

In addition to Mainous, the UF study team included members of the department of community health and family medicine at the College of Medicine: Frank A. Orlando, M.D., a clinical associate professor; Lu Yin, Ph.D., a data management analyst; Velyn L. Wu, M.D., an assistant clinical professor; and Aaron A. Saguil, M.D., a professor and of the department chair; as well as Pooja Sharma, a doctoral student in health services research at the College of Public Health and Health Professions.

For the UF study, researchers evaluated data from the National Health and Nutrition

“It is time to move beyond documenting the health problems that inflammation can cause to trying to fix these problems,” Mainous said.

JOURNAL

Frontiers in Medicine

DOI

10.3389/fmed.2023.1261083

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Inflammation and Poverty as Individual and Combined Predictors of 15-year Mortality Risk in Middle Aged and Older Adults in the US

ARTICLE PUBLICATION DATE

16-Jan-2024

Cannabis has no clear effect on treatment of opioid addiction, US study finds

Finding has significant implications for treatment programmes – with a growing number of states authorizing cannabis use to help opioid addiction

Peer-Reviewed Publication

TAYLOR & FRANCIS GROUP

Cannabis is not an effective treatment for opioid addiction, a new peer-reviewed study of thousands of people being treated for opioid use disorder suggests.

Experts, publishing their results today in The American Journal of Drug and Alcohol Abuse, have found that cannabis is having no significant effect on peoples’ use of opioids, taken outside of medical guidance.

The findings have substantial implications for U.S treatment programmes, some of which still require patients to abstain from cannabis before they qualify for potentially life-saving treatment. This is based on the belief they are more likely to use opioids non-medically if they are using cannabis.

The opposing, and increasingly popular, viewpoint, that cannabis can help wean people with opioid use disorder off opioids, is also called into question in this new study.

Opioids are effective painkillers, but they can also be addictive, and the U.S. remains in the grip of an opioid use disorder crisis.

Around 120 people die a day from drug overdoses involving opioids (prescription, such as oxycodone, and non-prescription, such as heroin) and opioid use disorder and related deaths cost the US economy more than $1 trillion a year.

As cannabis gains popularity among individuals with opioid use disorder in the U.S., its medicinal use is now legally recognized in thirty-seven states and Washington D.C. While pain remains the most common reason for medical cannabis authorization (i.e., “medical cannabis registration card”), an increasing number of states are adding “alternatives to opioids” or “opioid-treatable disorders” to their lists of approved conditions. In certain states, this includes treatment for opioid use disorder.

The study’s authors say this partly because the legalisation of the recreational use of cannabis in many states means the drug is being perceived as being less harmful than in the past. Some cannabis dispensaries have promoted medicinal cannabis as a treatment for opioid use disorder.

It isn’t clear, however, whether cannabis helps or hinders the treatment of opioid use disorder. Some studies have found it helps alleviate pain and opioid withdrawal, but others suggest it makes a return to opioids more likely.

“Clarifying how cannabis and opioids interact is crucial if we are to equip healthcare professionals to provide evidence-based addiction treatment, prevent overdose deaths and save lives,” says researcher Gabriel Costa, of University of Ribeirão Preto in Brazil.

Costa, under the mentorship of Dr. Joao P. De Aquino, of Yale University, and colleagues, carried out a systematic review and meta-analysis of existing research on the influence of cannabis on non-medical opioid use.

The meta-analysis combined the results of ten longitudinal studies involving 8,367 individuals who were receiving medication (buprenorphine, methadone or naltrexone) to treat their opioid use disorder.

As part of this, over the course of an average of 10 months, individuals were monitored for their non-medical opioid use – including the use of opioids not prescribed to them, taking more opioids than prescribed, or using opioids without a prescription.

The study compared the frequency of this use between individuals who used cannabis, typically obtained from non-regulated sources, and those who did not use cannabis.

Results showed there to be no link between cannabis use and rates of non-medical opioid use.

“Overall, we found no significant association between cannabis and non-medical opioid use among patients receiving pharmacotherapies for opioid use disorder,” states Costa.

“These findings neither confirm concerns about cannabis increasing non-medical opioid use in individuals being treated for opioid use disorder, nor do they endorse its efficacy in reducing non-medical opioid use.”

The implications for opioid use disorder treatment programmes are significant, adds Dr. De Aquino, who is a specialist in the treatment of persons with substance use disorders and co-occurring medical and psychiatric disorders.

He explains: “Our finding questions the ineffective practice of enforcing cannabis abstinence as a condition to offer life-saving medications for opioid use disorder.

“Our data suggests healthcare systems should instead adopt individualised treatment approaches which take into account each patient’s circumstances.

“This would include assessing cannabis use disorder, a problematic pattern cannabis use that affects a person’s wellbeing and ability to function, addressing pain management needs and treating co-occurring psychiatric conditions, such as depression and anxiety.”

Dr. De Aquino adds that there have been very few experimental studies into cannabis and its constituent cannabinoids’ ability to alleviate symptoms of opioid use disorder, and randomised placebo-controlled trials are needed to thoroughly assess its safety and effectiveness.

He says: “As high-potency synthetic opioids such fentanyl become increasingly available, it is of utmost importance that individuals with opioid use disorder have access to FDA-approved treatments.

“Methadone, buprenorphine, and extended-release intramuscular naltrexone – are known to be life-saving and are the cornerstone of opioid use disorder management.”

Limitations include a lack of consistency in how the studies in systematic review and meta-analysis were conducted. This includes differences in how cannabis and opioid use were measured and variations in baseline opioid use status.

In addition, although the results are applicable to general cannabis use, they may not apply to individuals with cannabis use disorder.

JOURNAL

The American Journal of Drug and Alcohol Abuse

DOI

10.1080/00952990.2023.2287406

METHOD OF RESEARCH

Systematic review

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The Impact of Cannabis on Non-Medical Opioid Use Among Individuals Receiving Pharmacotherapies for Opioid Use Disorder: A Systematic Review and Meta-Analysis of Longitudinal Studies

ARTICLE PUBLICATION DATE

16-Jan-2024

COVID-19 vaccine reduces long COVID in children

Vaccination associated with moderate protection in large, diverse cohort

Peer-Reviewed Publication

CHILDREN'S HOSPITAL OF PHILADELPHIA

Philadelphia, January 16, 2024 – Vaccination against SARS-CoV-2, the virus that causes COVID-19, reduces the risk of serious acute illness in children and adolescents. However, its role in protecting against persistent health problems in the months after COVID-19, or “long COVID,” was less clear. Now, researchers from 17 health systems in the U.S., in work led by investigators at the Children’s Hospital of Philadelphia (CHOP), have found that vaccination provides moderate protection against long COVID. Vaccination also has a stronger effect in adolescents, who have a higher risk of developing long COVID than young children.

The findings of the large retrospective study, based on electronic health records analyzed as part of the National Institutes of Health’s Researching COVID to Enhance Recovery (RECOVER) initiative, were published today in the journal Pediatrics.

While overall severity of COVID-19 has been lower in children than adults, the burden of long COVID has been difficult to accurately describe since the symptoms can vary widely and the exact ways the virus causes them are unknown. Some symptoms include brain fog, dyspnea, gastrointestinal dysfunction, generalized pain and fatigue, while others are more acute, like inflammatory reaction or heart problems.

“To date, no studies have assessed clinical data for large, diverse groups of children to address this important question,” said lead study author Hanieh Razzaghi, PhD, MPH, Director of Analytics in the PEDSnet and RECOVER/PCORnet EHR Coordinating Centers in the Applied Clinical Research Center at Children’s Hospital of Philadelphia. “Using clinical data from across health care networks allowed us to have a large enough sample of patients to identify rare effects of the virus and its impact on children.”

The researchers analyzed results from a large-scale collaboration of health systems from PCORnet® as part of the National Institutes of Health’s Researching COVID to Enhance Recovery (RECOVER) initiative, which was created to learn about the long-term effects of COVID-19. Data from 17 health systems were used to assess vaccine effectiveness against long COVID in two groups of patients between 5 and 11 years old and 12 and 17 years old, respectively, as well as the time period in which patients were impacted. The vaccination rate was 56% in the cohort of 1,037,936 children.

The incidence of probable long COVID was 4.5% among patients with COVID-19, though only 0.7% of patients were clinically diagnosed with long COVID. The study estimated effectiveness of the vaccine within 12 months of administration as 35.4% against probable long COVID and 41.7% against diagnosed long COVID. The estimate was higher in adolescents compared with younger children (50.3% vs. 23.8%), and higher at six months (61.4%) but decreased to 10.6% at 18 months. Children who were vaccinated after recovering from COVID-19 also appeared to benefit, with vaccine effectiveness of 46% against probable long COVID after a subsequent episode of COVID-19.

“This study provides us with important data showing the protective effects of the vaccine against long-haul COVID and suggests that this protection is mostly from preventing visible infections. We hope this means that as vaccines are improved to be more effective against current strains of SARS-CoV-2, their protection against long COVID will get better, too,” said senior study author Charles Bailey, MD, PhD, Associate Professor of Pediatrics and co-principal investigator for the PEDSnet and RECOVER/PCORnet EHR Coordinating Centers in the Applied Clinical Research Center at CHOP. “These retrospective data provide guidance for additional research into the ways long COVID develops, and how we can better protect children and adolescents.”

This study was supported by the National Institutes of Health (NIH) Agreement OT2HL161847-01 as part of the Researching COVID to Enhance Recovery (RECOVER) program of research.

Razzaghi et al, “Vaccine Effectiveness Against Long COVID in Children.” Pediatrics. Online January 16, 2024. DOI: 10.1542/peds.2023-064446.

About Children’s Hospital of Philadelphia:

A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.

JOURNAL

PEDIATRICS

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Vaccine Effectiveness Against Long COVID in Children

ARTICLE PUBLICATION DATE

16-Jan-2024

First all-UK study of 67 million people reveals consequences of missed COVID-19 vaccines

Peer-Reviewed Publication

HEALTH DATA RESEARCH UK

The first research study of the entire UK population highlights gaps in COVID-19 vaccine coverage. Between a third and a half of the populations of the four UK nations had not had the recommended number of COVID vaccinations and boosters by summer 2022.

Findings suggest that more than 7,000 hospitalisations and deaths might have been averted in summer 2022 if the UK had had better vaccine coverage, according to the paper, published today in The Lancet.

With COVID-19 cases on the rise and a new variant strain recently identified, this research provides a timely insight into vaccine uptake and hesitancy and could inform policy-makers.

The findings – led by Health Data Research UK (HDR UK) and the University of Edinburgh – relied on secure access to anonymised health data for everyone in all four nations of the UK, an advance which has only become possible during the pandemic. The researchers say that this approach could be extended to many other areas of medicine with great potential for new discoveries in the understanding and treatment of disease.

Professor Sir Aziz Sheikh, Director of the Usher Institute at the University of Edinburgh, HDR UK Research Director and study co-lead, said: “Large-scale data studies have been critical to pandemic management, allowing scientists to make policy-relevant findings at speed. COVID-19 vaccines save lives. As new variants emerge, this study will help to pinpoint groups of our society and areas of the country where public health campaigns should be focused and tailored for those communities.”

Early COVID-19 vaccine rollout began strongly in the UK, with over 90% of the population over the age of 12 vaccinated with at least one dose by January 2022. However, rates of subsequent booster doses across the UK were not fully understood until now.

Scientists from England, Scotland, Northern Ireland and Wales studied securely-held, routinely collected NHS data from everyone over 5 years of age during June 1 to September 30 2022. All data was de-identified and available only to approved researchers.

Data from across the four countries was then pooled and harmonised – or made more uniform – a feat that was not possible until now. People were grouped by vaccine status, with under-vaccination defined as not having had all doses of a vaccine for which that a person was eligible.

The findings reveal that the proportion of people who were under-vaccinated on June 1st 2022 ranged between one third and one half of the population – 45.7% for England, 49.8% for Northern Ireland, 34.2% for Scotland and 32.8% Wales.

Mathematical modelling indicated that 7,180 hospitalisations and deaths out of around 40,400 severe COVID-19 outcomes during four months in summer 2022 might have been averted, if the UK population was fully vaccinated.

Under-vaccination was related to significantly more hospitalisations and deaths across all age groups studied, with under-vaccinated people over 75 more than twice as likely to have a severe COVID-19 outcome than those who were fully protected.

The highest rates of under-vaccination were found in younger people, men, people in areas of higher deprivation, and people of non-white ethnicity.

Researchers say the study – the largest ever study carried out in the UK – also ushers in a new era for UK science by overcoming challenges in uniting NHS data that is gathered and stored in different ways between devolved nations.

Professor Cathie Sudlow, Chief Scientist at Health Data Research UK and Director of the British Heart Foundation (BHF) Data Science Centre, said: “The infrastructure now exists to make full use of the potential of routinely collected data in the NHS across the four nations of the UK. We believe that we could and should extend these approaches to many other areas of medicine, such as cancer, heart disease and diabetes to search for better understanding, prevention and treatment of disease."

The study was set up to provide UK and devolved governments with data-driven insights into COVID-19 vaccination coverage and establish data pooling methods and infrastructure to pave the way for future UK-wide studies. It is led by HDR UK and the University of Edinburgh, in collaboration with research teams from across the four nations.

Alan Keys, a public contributor at the British Heart Foundation (BHF) Data Science Centre at HDR UK who sat on the steering group of the study and is a co-author on the paper, said: “The research outcome is a powerful validation of the benefits of vaccination.”

Ends

Notes to Editors:

For further information, copies of the paper or to request an interview with the researchers, contact the HDR UK Communications team at media@hdruk.ac.uk or +44 7594 514007
Once published, the study will be available at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02467-4/fulltext
Health Data Research UK is the national institute for health data that includes England, Wales, Scotland and Northern Ireland. Its mission is to unite the UK’s health data to enable discoveries that improve people’s lives. It is a charity funded by UK Research and Innovation, the Department of Health and Social Care in England and equivalents in Northern Ireland, Wales and Scotland, and leading medical research charities. www.hdruk.ac.uk
The British Heart Foundation (BHF) Data Science Centre is a partnership between Health Data Research UK (HDR UK) and the British Heart Foundation. We work closely with patients, the public, NHS organisations, researchers, and clinicians to promote the safe and ethical use of data for research into the causes, prevention and treatment of all diseases of the heart and circulation. https://bhfdatasciencecentre.org/
Read more about the HDR UK COALESCE study here: https://www.ed.ac.uk/usher/eave-ii/connected-projects/coalesce

JOURNAL

The Lancet

DOI

10.1016/S0140-6736(23)02622-3

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

ARTICLE PUBLICATION DATE

15-Jan-2024

COI STATEMENT

Aziz Sheikh (ASh) reports being a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, the Scottish Government’s Standing Committee on Pandemic Preparedness, the UK Government’s New and Emerging Respiratory Virus Threats Advisory Group Risk Stratification Subgroup, the Department of Health and Social Care’s COVID-19 Therapeutics Modelling Group, and AstraZeneca’s COVID-19 Strategic Thrombocytopenia Taskforce (all unfunded). Prof C Robertson (CR) reports being a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, the Scientific Pandemic Influenza Group on Modelling, and the Medicines and Healthcare Products Regulatory Agency’s Vaccine Benefit and Risk Working Group. Declan T Bradley (DTB) reports being a member of the Scientific Pandemic Influenza Group on Modelling and the COVID-19 Scientific Advisory Group for Emergencies and its subgroups. Kamlesh Khunti (KK) reports being chair of the ethnicity subgroup of, and a member of, the UK Scientific Advisory Group for Emergencies. RAL reports being a member of the Welsh Government COVID-19 Technical Advisory Group. All other authors declare no competing interests.

Key moment in the evolution of life on Earth captured in fossils

Peer-Reviewed Publication

CURTIN UNIVERSITY

Curtin-led research has for the first time precisely dated some of the oldest fossils of complex multicellular life in the world, helping to track a pivotal moment in the history of Earth when the seas began teeming with new lifeforms - after four billion years of containing only single-celled microbes.

Lead author PhD student Anthony Clarke, from the Timescales of Mineral Systems Group within Curtin’s School of Earth and Planetary Sciences, said to determine the age of the fossils, researchers used volcanic ash layers like bookmarks in the geological sequence.

“Located in the Coed Cochion Quarry in Wales, which contains the richest occurrence of shallow marine life in Britain, we used outfall from an ancient volcano that blanketed the animals as a time marker to accurately date the fossils to 565 million years, accurate down to 0.1 per cent,” Mr Clarke said.

“With similar Ediacaran fossils found at sites around the world including in Australia, dating the fossils identifies them as being part of an ancient living community that developed as Earth thawed out from a global ice age.

“These creatures would in some ways resemble modern day marine species such as jellyfish, yet in other ways be bizarre and unfamiliar. Some appear fern-like, others like cabbages, whereas others resembled sea pens.”

Study co-author Professor Chris Kirkland, also from the Timescales of Mineral Systems Group at Curtin, said the fossils are named after the Ediacara Hills in South Australia’s Flinders Ranges, where they were first discovered, leading to the first new geological period established in over a century.

“These Welsh fossils appear directly comparable to the famous fossils of Ediacara in South Australia,” Professor Kirkland said.

“The fossils, including creatures like the disc-shaped Aspidella terranovica, showcase some of the earliest evidence of large-scale multicellular organisms, marking a transformative moment in Earth’s biological history.

“Ediacaran fossils record the response of life to the thaw out from a global glaciation, which shows the deep connection between geological processes and biology.

“Our study underscores the importance of understanding these ancient ecosystems in order to unravel the mysteries of Earth’s past and shape our comprehension of life’s evolution.”

Available online here once published, the full research paper, ‘U–Pb zircon-rutile dating of the Llangynog Inlier, Wales: constraints on an Ediacaran shallow 1 marine fossil assemblage from East Avalonia’ will appear in the.Journal of the Geological Society (JGS), which is owned and published by the Geological Society of London. JGS publishes topical, innovative and interdisciplinary research with global reach across the full range of Earth and planetary sciences.

JOURNAL

Journal of the Geological Society

DOI

10.1144/jgs2023-081

METHOD OF RESEARCH

Imaging analysis

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

U–Pb zircon-rutile dating of the Llangynog Inlier, Wales: constraints on an Ediacaran shallow 1 marine fossil assemblage from East Avalonia’

ARTICLE PUBLICATION DATE

15-Jan-2024