Friday, November 15, 2024

Specific long term condition combinations have major role in NHS ‘winter pressures’

Cardiovascular disease, cancer, kidney disease, diabetes quartet linked to 11-fold higher hospital admission risk. Kidney disease + cardiovascular disease + dementia + osteoarthritis linked to 24-fold higher death risk

BMJ Group

Specific combinations of long term conditions have a major role in the additional pressures the NHS faces every winter, because they are associated with significantly higher risks of hospital admissions and death, finds research published in the open access journal BMJ Medicine.

The risk of hospital admission was 11 times higher among those with the quartet of cancer, kidney disease, cardiovascular disease, and type 2 diabetes than it was among those without any of these long term conditions, the findings show.

And people with kidney disease, cardiovascular disease, dementia, and osteoarthritis were 24 times more likely to die as those who didn’t have these conditions.

Winter pressures are prompted by the worsening of health issues as a result of colder weather, seasonal viruses, increased isolation and loneliness, plus systems level difficulties caused by higher bed occupancy and staff absences, explain the researchers. These additional pressures usually cover the period from December 1 to March 31.

The number of people in England with 2 or more long term conditions is projected to include almost 70% of the population by 2035. And while previously published research has established the increased health service demand related to multiple long term conditions during the winter, it’s not clear exactly which combinations might be the most critical, say the researchers.

To try and find out, they reviewed routinely collected and linked primary and secondary care health data for adults in England, during the winter pressures period of 2021-22, to identify the reasons for hospital admission. This period coincided with the COVID-19 pandemic when health and social care services were substantially disrupted.

Complete data were available for 48.3 million people, just over half of whom were women (51%). Their average age was 49, and 81% of them were White.

The researchers selected 59 long term conditions which were categorised into 19 groups, based on feedback from clinicians, patients, and policy-makers.

During the study period, 4,710,675 hospital admissions and 176,895 deaths were recorded. Overall, nearly 20 million people (40.5%) had no long term conditions; 13.5 million (28%) had one; and nearly a third (15 million; 31%) had 2 or more.

Analysis of the data showed that particular combinations of long term conditions were associated with heightened risks of hospital admission and death.

After factoring in age, sex, ethnicity, and area based socioeconomic deprivation, people with cancer, kidney disease, cardiovascular disease, and type 2 diabetes were 11 times more likely to be admitted to hospital during the winter than those who didn’t have this combination.

Similarly, this risk was nearly 10 times higher for those with cancer, chronic kidney disease, cardiovascular disease, and osteoarthritis, and those with cancer, chronic kidney disease, and cardiovascular disease.

Among the 10 combinations that contributed to the highest rates of hospital admissions, cardiovascular disease featured in all but 1, chronic kidney disease in 8, and cancer in 6.

Analysis of the deaths linked to particular combinations of long term conditions showed that people with cardiovascular disease and dementia were nearly 15 times more likely to die than those with neither of these conditions.

And those with the combination of kidney disease, cardiovascular disease, dementia, and osteoarthritis were more than 24 times more likely to do so.

Cardiovascular disease featured in all 10 of the riskiest combinations, while chronic kidney disease featured in 7 of them.

Cardiovascular disease plus dementia also featured in all of the top 5 riskiest combinations, and this duo was associated with a substantially higher rate of death than many 3, 4, and 5 long term condition combinations.

This is an observational study, precluding firm conclusions to be drawn about causal factors. And the researchers acknowledge various limitations to their findings, including the lack of information about the length or severity of illness or frailty among those with long term conditions.

But they point out: “Current policy and clinical guidance consider the risk of hospital admission and death for multiple long term conditions during the winter season as one homogenous condition,” when this is clearly not the case.

And they suggest that the findings could help inform more targeted planning for winter pressures, enabling resources to be allocated where they are needed the most.

“Multimorbidity patterns are a major determinant of hospital admission and mortality during winter,” agree Dr Jonathan Batty and colleagues of the University of Leeds, in a linked editorial.

“In the broader context of winter pressures and increasing multimorbidity, [the study] underscores the need for methods that can identify individuals at high risk of preventable hospital admission and mortality, and strategies to mitigate the risk observed for those people with the most adverse combinations of long term conditions,” they conclude.

Journal

BMJ Medicine

DOI

10.1136/bmjmed-2024-001016

Method of Research

Observational study

Subject of Research

People

Article Title

Combinations of multiple long term conditions and risk of hospital admission or death during winter 2021-22 in England: population based cohort study

Article Publication Date

12-Nov-2024

COI Statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research (NIHR) for the submitted work; KK, CLG, FZ, and SS are supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM), NIHR Global Research Centre for Multiple Long-Term Conditions, the NIHR Leicester Biomedical Research Centre (BRC) and the British Heart Foundation Centre for Excellence; KK and HDM are supported by the Cross NIHR Collaboration for Multiple Long Term Conditions; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Making an impact. Research studies a new side of helmet safety: faceguard failures

Team of Clemson professors, students patents test to make sports helmets safer

Clemson University

There is a large window-lined laboratory in the back of one of Clemson University’s most storied buildings, Newman Hall, filled with machines that look like they were extracted straight from Dr. Jekyll’s lab. On one wall a contraption made of pullies and wires attached to the ceiling waits to drop objects and measure the impact; in the middle of the room, a giant metal base shakes a pallet of boxes in perpetuity; on the other side of the room sits what looks like a gigantic nut cracker big enough to squish a small car – but the most Medieval-looking area is the bay on the east side of the room full of machines designed to smack heads.

This is the Clemson Headgear Impact Performance (CHIP) Lab, where John DesJardins, a bioengineering professor, and Greg Batt, a food, nutrition, and packaging sciences associate professor, have spent nearly a decade working on a better way to test the strength of sports helmet faceguards.

The performance of faceguards and how it affects a helmet’s performance is woefully understudied, says DesJardins, and that’s why he and Batt created the CHIP Lab.

“The facemask connects to the helmet, and that connection is poorly studied,” he explained during a tour of the CHIP Lab on a quiet summer day on campus. “How does the rigidity of the mask affect the impact that you receive? When it gets hit, it spreads out; when it does that, it makes the helmet on your head wider, so it goes flying off. It completely changes the dynamics of the helmet. There are a lot of unknowns, and that’s why we decided to step in and bring those problems into the academic world.”

DesJardins says the project initially started with a call from Clemson graduate Jay Elmore ‘98, owner of Green Gridiron in Pendleton, the premier facemask reconditioner for top-level programs in the NFL, CFL, XFL, NCAA, semi-pro, high school and youth organizations.

“He had this machine in his facility in Pendleton and was having trouble on the engineering side keeping it up to date, doing the testing, and finding somebody qualified to operate it who was affordable enough to keep him in business,” explains DesJardins. “He said, ‘Please, take it!’ and donated the machine to us in exchange for us doing free testing for a couple of years. Ever since then, he’s been handing us boxes and boxes of facemasks.”

Batt says the CHIP Lab tests well over a 1000 masks a year as an ongoing testing service.

“Masks are made to protect from eye injuries, nose injuries, fingers coming through the mask and so on,” says Batt, noting there are about a dozen labs nationally that do this kind of testing, but the CHIP Lab is unique. “Students run the show here. They do all the testing and collect the data, and they come from a wide range of degree fields: bioengineering, packaging science, a couple of mechanical engineers, and we even have a physics major right now.”

When asked how often facemasks fail, Batt said it’s more often than one might think.

“That is an excellent question. We get some of that information from the equipment manager here for Clemson Football, Nick Yarid. He gives us his damaged masks. We might have a dozen and a half from a spring practice that don’t pass his test.”

“A good team will replace all of their masks every year just so they don’t have to worry about a potential miss, but that creates waste,” says DesJardins. “Also, many masks are over-manufactured. We’re looking at that as well. Why would you want to wear something heavier when you can wear something lighter and reduce waste?”

The original machine Elmore donated is a mean-looking device that drops a weighted human mannequin head attached to a guillotine-like blade onto a metal plate.

“It’s old-school and very low-tech,” says DesJardins. “And it’s a destructive test, which is the unfortunate aspect of it. The accelerometers measure the impact, which is not supposed to reach a certain threshold, and the facemask is not supposed to deform or intrude into the face area enough to bash your nose in or something. This test is designed to allow us to understand that, but we determined it’s really antiquated.”

DesJardins and Batt decided to invent a better, non-destructive way to get the same data.

They solicited for grant money and got a pneumatic impact ram that can smack fake heads in a much more realistic way.

“The NFL has impact standards for all the different orientations of the head and different speeds and for different player positions,” says DesJardins, picking up one of the plastic and metal heads used in the machine. “This weighs as much as a human head – about 12 pounds. You can rotate the head and the neck to different positions and angles, and there are accelerometers that measure the impact.”

DesJardins points to a large barrel attached by hinges to one side of the machine, “And just to make it super fun, you can rotate this sucker up, and it shoots hockey pucks!”

Using data gathered from whacking thousands of facemasks with the new ram, Batt and Desjardins teamed up with then-Ph.D. student Alex Bina ’22, now the director of applied science for the Clemson University Football Program, and invented a novel testing method that can put pressure on a facemask with precision and measure its strength without destroying it. They patented the technique in 2022.

“We thought, ‘What are you trying to get out of this test?’” says DesJardins. “Really, it’s taking a facemask and finding out how strong and stiff it is. We came up with a new method: a compression test that squishes it down just a little bit – about five millimeters – to determine its strength. You don’t need to bash helmets and facemasks in, which is not cheap.”

CURF, who is the technology transfer and innovation office for Clemson, filed for and received the patent (US Patent# 11,357,281). CURF also recently awarded DesJardins and Batt a Technology Maturation Grant to make a benchtop testing machine that they can market.

“Those are fancy words for, ‘You thought of it, now you have to make it,” laughs DesJardins.

The hope is the long-term influence of the data collected from their invention will make sports safer for everyone, from kids in pee-wee football to professional football and hockey players.

“Clemson University prides itself on supporting Translational Research, and the CHIP Lab embodies such a commitment,” says Bina. “I consider myself blessed because not many graduate students get to work on a multidisciplinary project at the interface between academia and industry. Combining principles of packaging science and bioengineering with industry need and technology transfer support via CURF, Dr. DesJardins and Dr. Batt allowed me to squeeze the most out of my education while developing innovative life-changing technology for a sport we all love.”

And they’re not stopping with facemasks. Batt and DesJardins already have plans to expand their research below the neck and into chest protection for athletes.

“We just received a grant to study commotio cordis, a rare disruption of heart rhythm that occurs as a result of a blow to the area directly over the heart at a critical instant during the cycle of a heartbeat,” says Batt. “Buffalo Bills safety Damar Hamlin famously collapsed from it during a Monday Night Football game in 2023.”

DesJardins says they just acquired a new instrumented torso that can record the impact force on the chest.

“Chest protection seems to be an important thing, to say the least, so we’re going to take that on next.”

Method of Research

Experimental study

Subject of Research

People

New Digital Dome launches in Joburg

University of the Witwatersrand

image:
The Wits Anglo Digital Dome
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Credit: Wits University

The Wits Anglo American Digital Dome - a place of infinite possibilities - will forever change how South Africans teach, research, and engage with science, technology, business, sport, the humanities and the arts, in a multidisciplinary facility.

The new Wits Anglo Digital Dome offers a 360° immersive experience for visitors of all ages, with a variety of shows for young and old. It will also serve as a modern teaching venue and a collaborative research space where scientists and students can visualise their work – be it in big data, astrophysics, the digital arts, artificial medicine, microbiology, or precision medicine.

The new Digital Dome will open to the public in February 2025. Visit the website at https://digitaldome.wits.ac.za/

[For the media: Download the media pack]

First completed in 1960, the old Planetarium was the first full sized Planetarium in Africa. The new Digital Dome is the largest of its kind in the southern hemisphere, made possible through an investment of R90 million from Anglo American and Wits University.

"For the past 64 years, the Planetarium has entertained, inspired and educated millions of visitors from Gauteng and beyond,” says Professor Zeblon Vilakazi (FRS), Vice-Chancellor and Principal of Wits University. “Personally, I visited the old Planetarium in 1981 at the height of apartheid. It left a huge and indelible mark on me, and I believe that it played a key role in igniting a scientific spark that led to me becoming a nuclear physicist. Through the Wits Anglo American Digital Dome, we hope to continue inspiring people from various disciplines including those working in climate modelling, artificial intelligence and the digital arts."

The development of Johannesburg is intrinsically intertwined with the origins and growth of Wits, Anglo American, and mining.

Duncan Wanblad, Chief Executive of Anglo American says: “At Anglo American, we see investment in tertiary education as vital for advancing knowledge, driving innovation, and boosting economic growth. Universities are hubs of research and development, producing skilled professionals who tackle global challenges and push technological and scientific boundaries. Infrastructure like the Digital Dome enable this progress, providing students with specialised skills, enhancing job prospects and earning potential while contributing to broader societal and economic transformation.”

He adds: “It is inspiring to witness the power of partnerships, which is even more invigorating through this initiative. We have a long history with Wits and Johannesburg, and we are proud of the efforts made to rebuild the City. The new Wits Anglo American Digital Dome is a demonstration of our legacy and continued commitment not only to this institution but to the nation as a whole. This new space is designed to inspire and ignite interest in the science, technology, engineering, and mathematics disciplines for generations to come.”

What’s new?

The original Zeiss projector has been replaced by 10 brand new digital projectors to render an 8k full dome resolution. Each projector has its own image generator, which is controlled by a master computer. The sound in the Digital Dome has also been upgraded to an 8.2 audio system. The refurbished facility includes the new digital projection and sound systems and auditorium seating, with the possible future creation of a Science and Technology Exploratorium. A new north wing expansion houses operational offices, exhibition areas, and specialised spaces for Digital Dome show planning and design.

“We have created a high-tech 360 immersive experience," says Dr Moumita Aich, the Head of the Wits Anglo American Digital Dome. “Visitors, students and researchers will enjoy an immersive experience and will feel as if they are part of the shows - whether they are gliding through the middle of the International Space Station or following a herd of wildebeest through the migrations in the Serengeti. These shows aim to entertain people of all ages, with different interests, using the latest technology – the possibilities are infinite.”

When does it open to the public?

The Wits Anglo American Digital Dome will enter a pilot phase from November to the end of January 2025 and is expected to open its doors to the broader public in February 2025. The first shows to be viewed in the Digital Dome include a set of six full dome shows, donated by the American Museum of National History.

In lieu of gifts for attendees of the launch event, Wits and Anglo American will make funds available that will allow access to learners from selected quintile 1 – 3 schools to attend shows at no cost at the Wits Anglo American Digital Dome in 2025.

And what’s next?

Wits is home to talented scholars, and it is important for Africans to develop our own content, within our own context. Phase 3 of the project entails building a wing which will house studios and look towards developing content locally in conjunction with the Wits School of Arts, Digital Arts, the Tshimologong Digital Innovation Precinct, and other partners. It will also link to Wits’ new AI Institute that will be launched on 19 November in the Digital Dome.

The Wits Anglo Digital Dome

Wits Anglo American Digital Dome front night sky

Wits Anglo American Digital Dome

Credit

Wits University

An advance toward inhalable mRNA medications, vaccines

American Chemical Society

Most people don’t enjoy getting shots for treatments or vaccines. So, researchers are working to create more medicines, such as those made from messenger RNA (mRNA), that can be sprayed and inhaled. A study in the Journal of the American Chemical Society reports steps toward making inhalable mRNA medicines a possibility. Researchers outline their improved lipid-polymer nanoparticle for holding mRNA that is stable when nebulized and successfully delivers aerosols (liquid droplets) in mice’s lungs.

mRNA medicines encode proteins that could treat or prevent a variety of illnesses, including lung diseases. However, these proteins are delicate and can’t enter cells by themselves. To get intact mRNA inside lung cells, tiny fatty spheres (known as lipid nanoparticles) can be used like suitcases to store and transport the components until they reach their final destination. However, early versions of fatty spheres for mRNA delivery won’t work for inhalable medications because the nanoparticles clump together or increase in size when sprayed into the air. To try to address this problem, previous researchers attached a polymer, such as polyethylene glycol, onto one of the particle’s fatty components, but this didn’t stabilize the resulting lipid nanoparticles enough.

Now, Daniel Anderson, Allen Jiang, Sushil Lathwal and colleagues have hypothesized that a different type of polymer, one with repeating units of positively and negatively charged components called a zwitterionic polymer, could create mRNA-containing lipid nanoparticles that can withstand nebulization (turning a liquid into a mist). The researchers synthesized a variety of lipid nanoparticles out of four ingredients: a phospholipid, cholesterol, an ionizable lipid, and lipids of different lengths attached to zwitterionic polymers of various lengths. Initial tests indicated that many of the resulting lipid nanoparticles efficiently held mRNA and didn’t change size during misting or after being misted.

Then in animal trials, the researchers determined that a lower-cholesterol version of the lipid nanoparticles with zwitterionic polymers was the optimal formulation for aerosol delivery. When transporting an mRNA encoding a luminescent protein, this nanoparticle produced the highest luminescence within the animals’ lungs and a uniform protein expression in the tissues, thereby demonstrating that it had the best ability to deliver inhaled mRNA. Mice given three airborne doses of the optimal nanoparticle over a 2-week period maintained consistent luminescent protein production without experiencing measurable inflammation in the lungs. The delivery method even worked in mice with a thick layer of mucus lining their airways, which was meant to model the lungs of people with cystic fibrosis. Taken together, the researchers say this set of results demonstrates the successful airborne delivery of mRNA using zwitterionic polymers in lipid nanoparticles. As a next step, they plan to conduct tests in larger animals.

The authors acknowledge funding from the U.S. National Institutes of Health, Sanofi (formerly Translate Bio), the Cystic Fibrosis Foundation, the Massachusetts Institute of Technology Undergraduate Research Opportunities Program, and the Koch Institute Support (core) Grant from the National Cancer Institute.

The authors have filed a patent on this technology. Some authors are founders of oRNA Therapeutics and Moderna, biotechnology companies that produce RNA and mRNA medicines, respectively.

The paper’s abstract will be available on Nov. 13 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/jacs.4c11347

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