Day: February 19, 2025

Older Patients can Inadvertently be Put at Risk When Taken off Anticoagulants

Photo by cottonbro studio

For patients with atrial fibrillation, the risk of stroke or heart attack from stopping anticoagulants usually outweighs the risk of bleeding, according to new findings from the University of Bath.

Clinicians often worry about the dangers of prescribing blood thinning medications to older patients, due to concerns about falls and major bleeding, however this new study suggests that for patients with the common heart condition atrial fibrillation (AF), the health risks of not taking these drugs are significantly higher than the risk of a life-threatening bleed.

AF is associated with a fivefold increase in the risk of stroke. It also increases the risk of heart attacks and death. Anticoagulants are highly effective in managing AF and preventing strokes and other complications.

Older people also tend to fall more frequently, with falls being a leading cause of injury among adults aged 65 and older. These can lead to serious injuries, such as hip fractures and head injuries.

However, the new study, published in Heart, found that contrary to popular medical belief, stopping anticoagulants for patients aged 75 and over does not change the risk of major bleeds. These findings are important for clinicians to factor into their prescribing behaviour, according to the study’s authors.

“Prescribers need to consider the increased risk to patients of coming off anticoagulants, including stroke,” said Dr Anneka Mitchell, who conducted the research from the University of Bath and is a visiting researcher at the University’s Department of Life Sciences.

Rising cases

Cases of AF are rising in all age groups but particularly among people aged 85 years and over. In this age group, the number of people diagnosed with the condition doubled in men from 11.6% to 22.1% between 2000 and 2016, and increased in women from 9.6% to 16.5%. There is no data available to show trends from 2016.

Though there is a large body of evidence to support the use of blood thinners for older people with AF, the new study is believed to be the first to measure patient outcomes when anticoagulant medication is stopped.

Dr Mitchell’s study analysed data from the UK Clinical Practice Research Datalink (a research dataset that includes anonymised patient data from some UK general practices) between 2013 and 2017, focusing on patients aged 75 and older who were newly prescribed anticoagulants.

It found that the risks of stroke and death were three times higher during periods when patients were not receiving anticoagulation therapy. The risk of heart attacks was nearly double compared with periods when patients were treated with anticoagulants.

Warfarin versus direct oral anticoagulants

Dr Mitchell believes that as well as concern about falls, many clinicians base their decisions to withhold anticoagulants on the historic experience of patients taking the anticoagulant warfarin.

This medication – the only available option for treating AF until 2012 – is associated with a complex medication regimen, along with dietary restrictions and frequent blood-tests, making treatment difficult for many older patients.

Since 2013, however, a new family of drugs called direct oral anticoagulants (DOACs) have become the first line option for most patients. DOACs are as effective and safe as warfarin – sometimes more so – and are far more straightforward to take.

Dr Mitchell said: “For example, apixaban (a DOAC) has a lower risk of significant bleeding than warfarin, so for many older patients with AF, this would be an excellent medication.

“Our findings highlight the critical need for clinicians to carefully consider the risks of stopping anticoagulation therapy in older patients. Despite concerns about bleeding, this study suggests that discontinuing anticoagulation does not significantly affect the risk of major bleeding but does increase the risk of serious events such as stroke and death.”

She added: “Both the risks and benefits of medication must be discussed fully with patients before a medic stops prescribing anticoagulants, so that both doctor and patient are making a shared and informed decision. This study underscores the importance of evaluating the consequences of deprescribing anticoagulants, particularly in older adults who are at higher risk of adverse outcomes.”

Impacting the lives of older patients

Dr Anita McGrogan who led the research team from the Department of Life Sciences at Bath, said: “Older patients were poorly represented in clinical trials that evaluated the efficacy and safety of DOACs before these products were licensed, and those who were included were healthier than many people in the target group for prescribing. Because of this, the safety of these medications for people aged 75-plus was not evaluated, and many chose to avoid prescribing them for older people.

“This study has produced important results that will have an impact on patients in the future. It has filled the information gap by looking at anonymous data on 20 167 people aged over 75 years, collected by GPs. It clearly demonstrates the value of using big data to investigate important clinical questions, especially in vulnerable populations.”

Dr Tomas Welsh, an academic geriatrician at Royal United Hospitals Bath and research & medical director at ReMind, hopes the new research will provide both clinicians and patients with better evidence to inform their decisions regarding anticoagulants. He noted that, until now, clinicians advising patients to stop taking blood thinners were unable to quantify the increased risk of stroke.

“These data help patients and clinicians have a firmer grasp of the risks that they are being exposed to,” he said.

Dr Welsh also stressed that new-generation blood thinners were not always the right course of action for frail, older people.

“Suspending any medication or reducing the use of multiple medications in a frailer older patient is always a nuanced and individual discussion,” he said.

Source: University of Bath

Mitochondria may Hold the Key to Curing Diabetes

Cells with nuclei in blue, energy factories in green and the actin cytoskeleton in red. Credit: NIH

A new study has revealed that abnormalities in mitochondria, the powerhouses of the cell, can affect the development and maturation of pancreatic beta cells, eventually leading to them no longer being able to produced. This opens to the door to possibly restoring their function – and reversing the course of type 2 diabetes.

Mitochondrial defects are associated with the development of diseases such as type 2 diabetes. Several studies have shown that insulin-producing pancreatic β-cells of patients with diabetes have abnormal mitochondria and are unable to generate energy. Yet, these studies were unable to explain why the cells behaved this way.

In a study published in Science, University of Michigan researchers used mice to show that dysfunctional mitochondria trigger a response that affects the maturation and function of β-cells.

“We wanted to determine which pathways are important for maintaining proper mitochondrial function,” said first author Emily M. Walker, PhD, a research assistant professor of internal medicine.

To do so, the team damaged three components that are essential for mitochondrial function: their DNA, a pathway used to get rid of damaged mitochondria, and one that maintains a healthy pool of mitochondria in the cell.

“In all three cases, the exact same stress response was turned on, which caused β-cells to become immature, stop making enough insulin, and essentially stop being β-cells,” Walker said. 

“Our results demonstrate that the mitochondria can send signals to the nucleus and change the fate of the cell.”

The researchers also confirmed their findings in human pancreatic islet cells.

Mitochondrial dysfunction affects several types of cells

Their results prompted the team to expand their search into other cells that are affected during diabetes.  

Losing your β-cells is the most direct path to getting type 2 diabetes. Through our study we now have an explanation for what might be happening and how we can intervene and fix the root cause.”

-Scott A. Soleimanpour, M.D.

“Diabetes is a multi-system disease – you gain weight, your liver produces too much sugar and your muscles are affected. That’s why we wanted to look at other tissues as well,” said Scott A. Soleimanpour, M.D., director of the Michigan Diabetes Research Center and senior author of the study.

The team repeated their mouse experiments in liver cells and lipid cells and saw that the same stress response was turned on. Both cell types were unable to mature and function properly.

“Although we haven’t tested all possible cell types, we believe that our results could be applicable to all the different tissues that are affected by diabetes,” Soleimanpour said.

Reversing mitochondrial damage could help cure diabetes

Regardless of the cell type, the researchers found that damage to the mitochondria did not cause cell death. 

This observation brought up the possibility that if they could reverse the damage, the cells would function normally.

To do so, they used a drug called ISRIB that blocked the stress response. They found that after four weeks, the β-cells regained their ability to control glucose levels in mice.

“Losing your β-cells is the most direct path to getting type 2 diabetes. Through our study we now have an explanation for what might be happening and how we can intervene and fix the root cause,” Soleimanpour said.

The team is working on further dissecting the cellular pathways that are disrupted and hope that they will be able to replicate their results in cell samples from diabetic patients.

Source: Michigan Medicine – University of Michigan

Global Action Needed to Solve the Medical Oxygen Crisis

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Targets for universal access, national roadmaps and more affordable and accessible care are vital to help fill the medical oxygen gap affecting more than half of the world’s population, according to a new global report.

The Lancet Global Health Commission report details for the first time how future investment in strengthening medical oxygen systems could have a huge impact by saving millions of lives and improving pandemic preparedness.

Almost 400 million children and adults require medical oxygen every year. More than five billion people, 60 per cent of the world’s population, don’t have access to safe and affordable medical oxygen services.

The Commission, co-chaired by Makerere University in Uganda, the International Centre for Diarrheal Disease Research (icddr,b) in Bangladesh, Murdoch Children’s Research Institute (MCRI) in Australia, Karolinska Institute in Sweden and the Every Breath Counts Coalition in the US was launched in 2022 against the backdrop of the COVID-19 pandemic. The Commission was tasked with submitting actionable recommendations for governments, industry, global health agencies, donors and the healthcare workforce.

MCRI Dr Hamish Graham said the COVID-19 pandemic had put a spotlight on the longstanding global inequities in accessing medical oxygen.

“Oxygen is required at every level of the healthcare system for children and adults with a wide range of acute and chronic conditions,” he said. Previous efforts, including the major investments in response to the COVID-19 pandemic, largely focused on the delivery of equipment to produce more oxygen, neglecting the supporting systems and people required to ensure it was distributed, maintained, and used safely and effectively.”

Dr Graham said channelling investments into national oxygen plans and bolstering health systems, including wider use of pulse oximeters (a small device that measures how much oxygen is in the blood), would help solve the medical oxygen crisis.

“We urgently need to make high-quality, pulse oximeters more affordable and widely accessible,” he said. Pulse oximeters are available in 54 per cent of general and 83 per cent of tertiary hospitals in low- and middle-income countries, with frequent shortages and equipment breakdowns.

“Concerningly, in these countries the devices are performed for only 20 per cent of patients presenting to general hospitals and almost never for those at primary healthcare facilities. We see the greatest inequities in small and rural government health facilities and across Sub-Saharan Africa.”

Dr Graham said the importance of medical oxygen must also be recognised and integrated into broader national strategies and pandemic preparedness and response planning.

“Governments should bring together public and private sector partners with a stake in medical oxygen delivery, including health, education, industry, energy and transport to design a system and set up a governance structure that supports the new Global Oxygen Alliance (GO₂AL) and replenishing The Global Fund with a strong oxygen access mandate,” he said.

Source: Murdoch Childrens Research Institute

Calorie Labels on Menus could Make Eating Disorders Worse

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Calorie labels on restaurant menus are negatively impacting people with eating disorders, according to a new study published in the BMJ Public Health.

The review, which is the first of its kind, is led by researchers at King’s College London. It found that individuals who have been diagnosed with an eating disorder changed their behaviours if presented with a menu featuring calorie labels.

This included avoiding restaurants, triggering eating disorder thoughts and paying more attention to calorie labels as identified by eye tracking research.

The research found that some people with eating disorders reported that seeing menu labels reinforced their eating disorder beliefs.

The study evaluated existing research to help build a picture of how nutritional labels on menus impact people with a lived experience of eating disorders or disordered eating. It reviewed 16 studies from the UK, US, Canada and Saudi Arabia which included 8,074 participants in total.

The study highlights that people with eating disorders can feel that eating disorders are perceived as less important in the light of obesity prevention policies.

However, physical health cannot be measured by a single indicator such as weight. Some argue that calorie labels can be seen as a blunt instrument to fix a complicated problem and that people with eating disorders could be losing out.

Food labelling came into force in England in 2022. Restaurants, take-aways and cafes with 250 employees or more must display the calories of the food and drink they sell on menus, online menus and take-away platforms. The measure was an attempt to curb rising obesity levels. The United States and Canada have also made calorie displays mandatory, however, few policies targeting obesity have considered the potential impact on eating disorders.

The eating disorder charity Beat estimates that at least 1.25 million people in the UK have an eating disorder. The number of people admitted to hospital with an eating disorder has risen approximately 7% each year since 2005 – 2006.

Senior author Dr Tom Jewell, Lecturer in Mental Health Nursing at King’s College London, said: “Our study highlights that people with lived experience of eating disorders are frustrated at being left out of the conversation around calorie labels.”

Striking a balance between the positive and harmful impacts of calorie labels on menus is vital in any public health policies.Dr Tom Jewell, Senior author and Lecturer in Mental Health Nursing at King’s College London

“Policymakers should consider the impact on both obesity and eating disorders when making decisions about nutrition labelling. A recent review found that calorie labelling has a modest effect on people’s behaviour but this needs to be counterbalanced with the potential harm it does for people with eating disorders.”

Co-author Dr Nora Trompeter, Research Fellow University College London, said: “Our study provides an important addition to the evidence base around calorie labels.”

Typically, there is a lot of focus on whether policies are effective in reducing obesity, but it is also critical to investigate whether these policies inadvertently harm people with eating disorders.

“Our review also shows that more research is needed to fully understand the impact of calorie labels on individuals with eating disorders. For example, none of the studies included young people.”

Source: King’s College London

‘Healthy’ Vitamin B12 Levels not Enough to Ward off Neuro Decline

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Meeting the minimum requirement for vitamin B12, needed to make DNA, red blood cells and nerve tissue, may not actually be enough – particularly if for older adults. It may even put them at risk for cognitive impairment, according to a study published in Annals of Neurology.

The research found that older, healthy volunteers, with lower concentrations of B12, but still in the normal range, showed signs of neurological and cognitive deficiency. These levels were associated with more damage to the brain’s white matter – the nerve fibres that enable communication between areas of the brain – and test scores associated with slower cognitive and visual processing speeds, compared to those with higher B12.

The UC San Francisco researchers, led by senior author Ari J. Green, MD, of the Departments of Neurology and Ophthalmology and the Weill Institute for Neurosciences, said that the results raise questions about current B12 requirements and suggest the recommendations need updating.

“Previous studies that defined healthy amounts of B12 may have missed subtle functional manifestations of high or low levels that can affect people without causing overt symptoms,” said Green, noting that clear deficiencies of the vitamin are commonly associated with a type of anaemia. “Revisiting the definition of B12 deficiency to incorporate functional biomarkers could lead to earlier intervention and prevention of cognitive decline.”

Lower B12 correlates with slower processing speeds, brain lesions

In the study, researchers enrolled 231 healthy participants without dementia or mild cognitive impairment, whose average age was 71. They were recruited through the Brain Aging Network for Cognitive Health (BrANCH) study at UCSF.

Their blood B12 amounts averaged 414.8pmol/L, well above the U.S. minimum of 148pmol/L. Adjusted for factors like age, sex, education and cardiovascular risks, researchers looked at the biologically active component of B12, which provides a more accurate measure of the amount of the vitamin that the body can utilize. In cognitive testing, participants with lower active B12 were found to have slower processing speed, relating to subtle cognitive decline. Its impact was amplified by older age. They also showed significant delays responding to visual stimuli, indicating slower visual processing speeds and general slower brain conductivity.

MRIs revealed a higher volume of lesions in the participants’ white matter, which may be associated with cognitive decline, dementia or stroke.

While the study volunteers were older adults, who may have a specific vulnerability to lower levels of B12, co-first author Alexandra Beaudry-Richard, MSc, said that these lower levels could “impact cognition to a greater extent than what we previously thought, and may affect a much larger proportion of the population than we realize.” Beaudry-Richard is currently completing her doctorate in research and medicine at the UCSF Department of Neurology and the Department of Microbiology and Immunology at the University of Ottawa.

“In addition to redefining B12 deficiency, clinicians should consider supplementation in older patients with neurological symptoms even if their levels are within normal limits,” she said. “Ultimately, we need to invest in more research about the underlying biology of B12 insufficiency, since it may be a preventable cause of cognitive decline.”

Source: University of California – San Francisco