Categories : Medical Industry Mental HealthTags :

Stress, Overwork, Understaffing Driving Healthcare Workers from NHS

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Photo by Usman Yousaf on Unsplash

Work stress, high workload, and understaffing are the primary factors driving health professionals out of the NHS, suggest the results of a survey published in the open access journal BMJ Open.

The findings prompt the researchers to suggest that pay increases alone may not be sufficient to fix NHS staff retention. The NHS is short of well over 100 000 staff and fallout from COVID-19 has seen worsening retention.

The researchers investigated the ‘push’ factors behind decisions to leave the NHS, and whether these were ranked differently by profession and NHS setting, a year after exposure to the effects of the pandemic.

In 2021, NHS health professionals completed an online survey to determine the relative importance they gave to 8 factors as the key reasons for leaving NHS employment.

The respondents included 227 doctors; 687 nurses/midwives; 384 healthcare assistants and other nursing support staff; 417 allied health professionals, such as physiotherapists and occupational therapists; and 243 paramedics from acute, mental health, community, and ambulance services.

Using the paired comparison technique, whereby two push factors at a time were presented at a time, respondents were asked: ‘Which of these two factors is the bigger influence on why staff in your profession/job role leave the NHS’?’

Photo by Pavel Danilyuk

Compared to other professions, paramedics gave a much higher relative weighting to work stress, work-life balance, work intensity and pay higher relative weighting.

The factors compared were: staffing levels; working hours; mental health/stress; pay; time pressure; recognition of contribution; workload intensity; and work–life balance.

Compared to other professions, paramedics gave a much higher relative weighting to work stress, work-life balance, work intensity and pay higher relative weighting. Paramedics also ranked work-life balance as a stronger driver to leave the NHS. They ranked this second compared to a fourth or fifth ranking across the other professions.

Pay was considered more important by healthcare assistants and other nursing support staff and paramedics, but was generally ranked fourth or fifth by other professional groups. 

This contrasts with “some contemporary media and industrial relations accounts, and some academic research findings,” say the researchers, who nevertheless add: “While other variables appear to exert a stronger push than pay, this is not grounds to diminish it as a potential source of dissatisfaction in absolute terms.” 

Overall, health professionals ranked work-related stress, workload intensity, and staffing levels as the primary ‘push factors’ underpinning decisions to leave the NHS. Recognition of effort and working hours were ranked lowest. But there were differences in the order of importance and relative weighting given to the push factors among the different health professions.

Work intensity in acute care hospitals and community services; time pressure in community services; and recognition of effort in mental health services were given higher relative weightings.

“In common with the NHS annual staff survey and all other voluntary participation employee surveys, the potential for self-selection response bias cannot be discounted,” emphasise the researchers. 

But they conclude: “Excepting paramedics, rankings of leave variables across the different health professional families exhibit a high degree of alignment, at the ordinal level, and highlight the primacy of psychological stress, staff shortages, and work intensity.”

They add: “While increases in pay are transparently important to NHS staff, findings from this research suggest that enhancements in that domain alone may produce a modest impact on retention.

“An equivalent conclusion might be drawn with respect to the current high-profile emphasis on increased access to flexible working hours as a solution within contemporary NHS staff retention guidance to employers. 

“Both have potential to do good, but there are grounds for inferring there is a risk that neither may deliver sufficient good to redress the high and rising exodus in the absence of attention to what present as more fundamental factors driving exit.” 

Source: BMJ Open

Categories : Injury & TraumaTags :

SA’s Injury Statistics are not Accurate, Experts Warn

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Photo by Maxim Hopman on Unsplash

By Sonia A. Rao for GroundUp

Reporting of gun crime in South Africa is wildly inaccurate, work by the South African Medical Research Council (SAMRC) suggests. This is because the official death notification form does not distinguish between gun deaths from accidents and gun deaths from homicide.

The SAMRC has called on the government to update the country’s official death notification form. In a September 2023 South African Medical Journal (SAMJ) editorial, researchers and scientists Pam Groenewald, Richard Matzopoulos, Estevão Afonso and Debbie Bradshaw, say the form does not comply with international standards. While the World Health Organisation recommends reporting manner of death on the medical certificate for cause of death, South Africa’s form does not allow this, they say.

As a result, South Africa does not have accurate information on injury statistics, says Groenewald, a specialist scientist at SAMRC.

“Given that South Africa has got a really high injury burden, this is really not acceptable,” she said.

The SAMRC has pointed out that accurate, timely mortality data for natural and non-natural deaths is especially important after the Covid pandemic.

In a press release, the SAMRC said natural deaths had spiked during Covid waves, while injuries had fallen during government-imposed lockdowns and alcohol sales bans. “Of particular concern is the significant impact of alcohol bans on injury-related deaths,” the council said.

The release also said the statistics are necessary to develop and monitor programs to reduce injuries and violence, and track Sustainable Development Goals of road traffic injury reduction, gender equality and reducing violence-related death rates.

South Africa’s official mortality statistics overestimate accidental injuries and underestimate homicides, transport and suicide deaths, according to a research report also published in the September 2023 SAMJ.

In official death notification form data from Stats SA for 2017, nearly 99% of firearm deaths were classified as accidental and only 1% as homicide. But the SAMRC’s National Cause-of-Death Validation Project (NCoDV) found more than 88% of firearm deaths were homicide, and its Injury Mortality Survey (IMS) found more than 93%.

Similar differences occurred for suicides. Only 0.3% of firearm deaths were recorded as suicide in the 2017 Stats SA data, but they were recorded as 7% in NCoDV and IMS data.

The research report says NCoDV and IMS provide more detailed and consistent data on causes of injury than the death notification form, but they are costly and time-consuming, and not feasible for routine surveillance.

“It costs a lot of money, when we could be getting this data in with every death certificate that gets completed,” Groenewald says.

She says the SAMRC has been asking for an updated death certificate form since 2012.

No annual mortality report since 2018

Also, Stats SA has not published an updated mortality report since the pandemic. The last official report was released in 2021 for the year 2018.

“We’ve got no cause-of-death data at all, not just injuries, nothing. We haven’t seen a death certificate from during the Covid period; we don’t know what doctors have reported,” she said. “It’s mind boggling.”

Felicia Sithole, deputy director of media relations for Stats SA, said in a statement that the Mortality and Causes of Death report had been delayed by a backlog of processing death notification forms as a result of the Covid lockdown, and because of Census 2022 work.

Sithole said Stats SA is committed to publishing the 2019 and 2020 Mortality and Causes of Death reports by the end of March 2024.

“Stats SA fully comprehends the importance of the Mortality and Causes of Death release, especially during the Covid-19 pandemic, and acknowledges that our data must conform to international standards,” she said.

The SAMRC report also calls for the dormant National Forensic Pathology Services Committee to be reactivated. This would help improve data quality, the report says. The committee, established in 2014, has been inactive since 2018/9.

Foster Mohale, a media officer for the Department of Health, said the Minister of Health is in the process of appointing a new National Forensic Pathology Services Committee.

The Department of Home Affairs had not responded to requests for comment at the time of publication.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Injury & TraumaTags :

Students Develop an AI Tool that Predicts Survival of Brain Injury in ICU

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Photo by Anna Shvets on Pexels

A pair of postgraduate students have developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury. The two researchers combined functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques to tackle one of the most complex issues in critical care. They describe the new technology in the Journal of Neurology.

Whether it is the result of a stroke, cardiac arrest or traumatic brain injury, lives can forever be changed by a serious brain injury. But the potential of a good recovery is highly uncertain.

The University of Western Ontario researchers, Matthew Kolisnyk and Karnig Kazazian, are PhD candidates at Schulich School of Medicine & Dentistry in the lab of neuroscientist Adrian Owen.

“For years we’ve lacked the tools and techniques to know who is going to survive a serious brain injury,” said Owen.

An interdisciplinary team of researchers from Western, in collaboration with neurologists at London Health Sciences Centre and Lawson Health Research Institute sought to find a solution to this problem. They were led by Loretta Norton, a psychology professor at King’s University College at Western, who was one of the first researchers in the world to measure brain activity in the ICU.

The team measured brain activity in 25 patients at one of London’s two ICUs in the first few days after a serious brain injury and tested whether it could predict who would survive and who would not.

“We previously found that information about the potential for recovery in these patients was captured in the way different brain regions communicate with each other,” said Norton. “Intact communication between brain regions is an important factor for regaining consciousness.”

The breakthrough occurred when the team realized they could combine this imaging technique with an application of AI known as machine learning. They found they could predict patients who would recover with an accuracy of 80 per cent, which is higher than the current standard of care.

“Modern artificial intelligence has shown incredible predictive capabilities. Combining this with our existing imaging techniques was enough to better predict who will recover from their injuries,” said Kolisnyk.

While encouraging, the researchers say the prediction was not perfect and needs further research and testing.

“Given that these models learn best when they have lots of data, we hope our findings will lead to further collaborations with ICUs across Canada,” said Kazazian.

Source: University of Western Ontario

Categories : Implants and Prostheses NeurologyTags :

A New Way to Map the Human Auditory Pathway

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Photo by Brett Sayles

Researchers have developed a non-invasive method for mapping the human auditory pathway, which could potentially be used as a tool to help clinicians decide the best surgical strategy for patients with profound hearing loss. The findings, published online in the journal eLife, highlight the importance of early interventions to give patients the ability to hear and understand speech, so that their auditory-language network can develop properly and their long-term outcomes are improved.

Sensorineural hearing loss (SNHL) occurs when the sensitive hair cells inside the cochlea are damaged, or when there is damage to the auditory nerve which transmits sound to the brain. A person with profound hearing loss is typically unable to hear any sounds, or at best, only very loud sounds. Congenital SNHL has increased in prevalence over the past two decades, from 1.09 to 1.7 cases per 1000 live births.

The sound of speech is carried through the brain by nerve fibres in regions known as the auditory pathway, and are processed in a region called the language network. In cases of congenital SNHL, the lack of speech inputs reaching the language network may hinder its proper development, leading to poorer spoken language skills.

Currently, the primary treatments for profound SNHL are cochlear and auditory brainstem implantation, where a device is used to stimulate the peripheral cochlea or the central cochlear nucleus, respectively. Both techniques can partially restore hearing in patients, but their language development outcomes can vary. This is especially true for patients with inner ear malformations (IEM) or cochlear nerve deficiencies (CND), which contribute to 15-39% of congenital SNHL cases.

“Where SNHL is caused by CNDs and/or IEMs, there is a great deal of uncertainty around the best method of treatment. This is due to the difficulty of assessing the condition of the cochlear nerve and distinguishing between certain types of IEM, both of which impact surgical decision making,” says senior authors Hao Wu, a professor and Chief Physician specialising in Otolaryngology at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, China. Wu also serves as the Hospital Administrator and the Clinical and Academic Lead for the department. “We therefore need a more effective method for mapping the auditory pathway and diving deeper into how IEMs and CNDs affect the development of the auditory-language network.”

In their study, professor Wu’s team investigated the auditory and language pathways in 23 children under the age of six. They included 10 children with normal hearing, and 13 with profound SNHL. In the latter group, seven children had received cochlear implantations, two had received auditory brainstem implantations, and four were candidates for auditory brainstem implantations.

The human auditory pathway is difficult to investigate non-invasively due to its delicate and intricate subcortical structures located deep within the brain. To navigate this, the team developed a new methodology to reconstruct the pathway. First, they segmented the subcortical auditory structures using track density imaging, which are reconstructed from a specific type of MRI scan and provide much greater detail and information on the structural connectivity of the brain. This allowed them to delineate the cochlear nucleus and the superior olivary complex of the auditory pathway. They then tracked the auditory and language pathways using a neuroimaging technique called probabilistic tractography, which uses the information from an MRI scan to provide the most likely view of structural brain connectivity. Next, the team assessed the density and cross-section of the nerve fibres in the auditory and language pathways.

This combined methodology allowed them to investigate three key areas to inform surgical decision making: the condition of the nerve fibres in the auditory-language network of children with profound SNHL; the potential impact of IEMs and CNDs on the development of the network before surgical intervention; and the relationship between the pre-implant structural development of the network and the auditory-language outcomes following implantation.

The team’s observations revealed a lower nerve fibre density in children with profound SNHL, in comparison to those with normal hearing. This reduction was most pronounced in two regions of the inferior central auditory pathway, as well as the left language pathway.

In addition, the findings revealed that the language pathway is more sensitive than the central auditory system to IEMs and/or CNDs, implying that the structural development of the language pathway is more negatively impacted by the condition of the peripheral auditory structure. However, the authors caution that further study is required to validate this finding. As it is more difficult to image the central auditory pathway than the language pathway, this difference could have arisen due to the limitations of current neuroimaging technologies.

The authors say the study is also limited by a relatively small cohort of patients and an incomplete genetic dataset, so more studies with a more diverse patient population will also be needed. But with further validation, they add that the methodology could be used more widely for informing decisions in treating profound SNHL.

Source: eLife

Categories : Gender Mental HealthTags :

Inflammatory Markers of Depression Risk Differ in Boys and Girls

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New research led by King’s College London researchers has found that depression and the risk of depression are linked to different inflammatory cytokines in boys and girls. Previous research has shown that higher levels of inflammatory cytokines are associated with depression in adults, but little is known about this relationship in adolescence.

This study, published in the Journal of Affective Disorders, found that different cytokines were implicated in depression risk and severity in boys compared to girls. The research was part of the IDEA (Identifying Depression Early in Adolescence) project funded by MQ Mental Health Research.

To assess inflammation, researchers measured the blood cytokine levels in 75 adolescent boys and 75 adolescent girls (aged 14–16 years) from Brazil. The 150 participants had been recruited into three groups with equal numbers (50 participants in each group: 25 girls and 25 boys). The groups were those at low-risk for depression and not depressed, those at high risk of depression and not depressed, and those currently experiencing major depressive disorder (MDD).

The findings indicated that there are sex differences between the individual cytokines that are associated with depression in adolescents. Higher levels of the cytokine interleukin-2 (IL-2) were associated with both increased risk for depression and the severity of depressive symptoms in boys, but not in girls. However, higher levels of IL-6 were associated with severity of depression in girls, but not boys. In boys the levels of IL-2 were higher in the high-risk than the low-risk group and even higher in the group diagnosed with depression, indicating that in boys IL-2 levels in the blood could help indicate the onset of future depression.

Dr Zuzanna Zajkowska, Postdoctoral Researcher at King’s IoPPN and first author of the study, said: “This is the first study to show differences between boys and girls in the patterns of inflammation that are linked to the risk and development of adolescent depression.

“We found that the severity of depressive symptoms was associated with increased levels of the cytokine interleukin-2 in boys, but interleukin-6 in girls. We know more adolescent girls develop depression than boys and that the disorder takes a different course depending on sex so we hope that our findings will enable us to better understand why there are these differences and ultimately help develop more targeted treatments for different biological sexes.”

Researchers recruited adolescents from public schools in Brazil. Risk of depression was assessed by a composite risk score for depression based on 11 sociodemographic variables that had been developed as part of the IDEA project. Adolescents completed several questionnaires, self-reporting their emotional difficulties, relationships, experiences, and mood. They also completed a clinical assessment with a child and adolescent psychiatrist.

Senior author on the study Professor Valeria Mondelli, Clinical Professor of Psychoneuroimmunology at King’s IoPPN and theme-lead for Psychosis and Mood Disorders at the NIHR Maudsley BRC, said:

“Our findings suggest that inflammation and biological sex may have combined contribution to the risk for depression. We know that adolescence is a key time when many mental disorders first develop and by identifying which inflammatory proteins are linked to depression and how this is different between boys and girls we hope that our findings can pave the way to understanding what happens at this critical time in life. Our research highlights the importance of considering the combined impact of biology, psychology, and social factors to understand the mechanisms underlying depression.”

Source: King’s College London

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Plant Compound could Prove to be a Potent Tool against Candida

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A new study published in the journal ACS Infectious Diseases has found that a natural compound found in many plants inhibits the growth of drug-resistant Candida fungi – including its most virulent species, Candida auris, an emerging global health threat.

Led by Emory University researchers, the study used in vitro experiments that showed that the natural compound, a water-soluble tannin known as PGG, blocks 90% of the growth in four different species of Candida fungi. The researchers also discovered the mechanism by which PGG inhibits the growth: It grabs up iron molecules, essentially starving the fungi of an essential nutrient.

By starving the fungi rather than attacking it, the PGG mechanism does not promote the development of further drug resistance, unlike existing antifungal medications. In vitro testing also showed minimal toxicity of PGG to human cells.

“Drug-resistant fungal infections are a growing healthcare problem but there are few new antifungals in the drug-development pipeline,” says Cassandra Quave, senior author of the study and assistant professor at Emory University. “Our findings open a new potential approach to deal with these infections, including those caused by deadly Candida auris.”

C. auris is often multidrug-resistant and has a high mortality rate, leading the Centers for Disease Control and Prevention (CDC) to label it a serious global health threat.

“It’s a really bad bug,” says Lewis Marquez, first author of the study and a graduate student in Emory’s molecular systems and pharmacology programme. “Between 30 to 60% of the people who get infected with C. auris end up dying.”

An emerging threat

Some species of Candida, a yeast commonly found on the skin or in the digestive tract, can cause infection, which can be invasive and life-threatening. Immunocompromised people, including many hospital patients, are most at risk for invasive Candida infections, which are rapidly evolving drug resistance.

In 2007, the new Candida species, C. auris, emerged in a hospital patient in Japan. Since then, C. auris has caused health care-associated outbreaks in more than a dozen countries around the world with more than 3000 clinical cases reported in the United States alone.

A ‘natural’ approach to drug discovery

Quave is an ethnobotanist, studying how traditional people have used plants for medicine to search for promising new candidates for modern-day drugs. Her lab curates the Quave Natural Product Library, which contains 2500 botanical and fungal natural products extracted from 750 species collected at sites around the world.

“We’re not taking a random approach to identify potential new antimicrobials,” Quave says. “Focusing on plants used in traditional medicines allows us to hone in quickly on bioactive molecules.”

Previously, the Quave lab had found that the berries of the Brazilian peppertree, a plant used by traditional healers in the Amazon for centuries to treat skin infections and some other ailments, contains a flavone-rich compound that disarms drug-resistant staph bacteria. They had also found that the leaves of the Brazilian peppertree contain PGG, a compound that has shown antibacterial, anticancer and antiviral activities in previous research.

A 2020 study by the Quave lab, for instance, found that PGG inhibited growth of Carbapenem-resistant Acinetobacter baumannii, a bacterium that infects humans and is categorised as one of five urgent threats by the CDC.

The Brazilian peppertree is a member of the poison ivy family. “PGG has popped up repeatedly in our laboratory screens of plant compounds from members of this plant family,” Quave says. “It makes sense that these plants, which thrive in really wet environments, would contain molecules to fight a range of pathogens.”

Experimental results

The Quave lab decided to test whether PGG would show antifungal activity against Candida.

In vitro experiments demonstrated that PGG blocked around 90% of the growth in 12 strains from four species of Candida: C. albicans, multidrug-resistant C. auris and two other multidrug-resistant non-albicans Candida species.

PGG is a large molecule known for its iron-binding properties. The researchers tested the role of this characteristic in the antifungal activity.

“Each PGG molecule can bind up to five iron molecules,” Marquez explains. “When we added more iron to a dish, beyond the sequestering capacity of the PGG molecules, the fungi once again grew normally.”

Dish experiments also showed that PGG was well-tolerated by human kidney, liver and epithelial cells.

“Iron in human cells is generally not free iron,” Marquez says. “It is usually bound to a protein or is sequestered inside enzymes.”

A potential topical treatment

Previous animal studies on PGG have found that the molecule is metabolised quickly and removed from the body. Instead of an internal therapy, the researchers are investigating its potential efficacy as a topical antifungal.

“If a Candida infection breaks out on the skin of a patient where a catheter or other medical instrument is implanted, a topical antifungal might prevent the infection from spreading and entering into the body,” Marquez says.

The researchers will bext test PGG as a topical treatment for fungal skin infections in mice.

Meanwhile, Quave and Marquez have applied for a provisional patent for the use of PGG for the mitigation of fungal infections.

“These are still early days in the research, but another idea that we’re interested in pursuing is the potential use of PGG as a broad-spectrum microbial,” Quave says. “Many infections from acute injuries, such as battlefield wounds, tend to be polymicrobial so PGG could perhaps make a useful topical treatment in these cases.”

Source: Emory University

Categories : Cancer Skeletal SystemTags :

Why Tumours so Often Metastasise to the Spine

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The vertebral bones that constitute the spine are derived from a distinct type of stem cell that secretes a protein favouring tumour metastases, according to a study led by researchers at Weill Cornell Medicine. The discovery, published in Nature, opens up a new line of research on spinal disorders and helps explain why solid tumours so often spread to the spine, and could lead to new orthopaedic and cancer treatments.

Vertebral bone was found to be derived from a stem cell that is different from other bone-making stem cells. Using bone-like “organoids” made from vertebral stem cells, they showed that the known tendency of tumours to spread to the spine rather than long bones is due largely to a protein called MFGE8, secreted by these stem cells.

“We suspect that many bone diseases preferentially involving the spine are attributable to the distinct properties of vertebral bone stem cells,” said study senior author Dr Matthew Greenblatt.

In recent years, Dr Greenblatt and other scientists have found that different types of bone are derived from different types of bone stem cells. Since vertebrae develop along a different pathway early in life, and also appear to have had a distinct evolutionary trajectory, Dr Greenblatt and his team hypothesised that a distinct vertebral stem cell probably exists.

The researchers started out by isolating what are broadly known as skeletal stem cells, which give rise to all bone and cartilage, from different bones in lab mice based on known surface protein markers of such cells. They then analysed gene activity in these cells to see if they could find a distinct pattern for the ones associated with vertebral bone.

This effort yielded two key findings. The first was a new and more accurate surface-marker-based definition of skeletal stem cells as a whole. This new definition excluded a set of cells that are not stem cells that had been included in the old stem cell definition, thus clouding some prior research in this area.

The second finding was that skeletal stem cells from different bones do indeed vary systematically in their gene activity. From this analysis, the team identified a distinct set of markers for vertebral stem cells, and confirmed these cells’ functional roles to form spinal bone in further experiments in mice and in lab-dish cell culture systems.

The researchers next investigated the phenomenon of the spine’s relative attraction for tumour metastases, including breast, prostate and lung tumours, compared to other types of bone. The traditional theory, dating to the 1940s, is that this “spinal tropism” relates to patterns of blood flow that preferentially convey metastases to the spine versus long bones. But when the researchers reproduced the spinal tropism phenomenon in animal models, they found evidence that blood flow isn’t the explanation, finding instead a clue pointing to vertebral stem cells as the possible culprits.

“We observed that the site of initial seeding of metastatic tumour cells was predominantly in an area of marrow where vertebral stem cells and their progeny cells would be located,” said study first author Dr Jun Sun, a postdoctoral researcher in the Greenblatt laboratory.

Subsequently, the team found that removing vertebral stem cells eliminated the difference in metastasis rates between spine bones and long bones. Ultimately, they determined that MFGE8, a protein secreted in higher amounts by vertebral compared to long bone stem cells, is a major contributor to spinal tropism. To confirm the relevance of the findings in humans, the team collaborated with investigators at Hospital for Special Surgery to identify the human counterparts of the mouse vertebral stem cells and characterise their properties.

The researchers are now exploring methods for blocking MFGE8 to reduce the risk of spinal metastasis in cancer patients. More generally, said Dr Greenblatt, they are studying how the distinctive properties of vertebral stem cells contribute to spinal disorders.

“There’s a subdiscipline in orthopaedics called spinal orthopaedics, and we think that most of the conditions in that clinical category have to do with this stem cell we’ve just identified,” Dr Greenblatt said.

Source: Weill Cornell Medicine

Categories : Cardiovascular Disease Metabolic DisordersTags :

New Research Points to Clot Lysis Protein for Cholesterol Control

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Source: Wikimedia CC0

While high levels of low-density lipoprotein (LDL) can be reduced by drugs such as statins, reducing the risk of myocardial infarction and stroke, risk still remains in the form of other cholesterols. New research published in the journal Science describes how manipulating a protein involved in blood clot lysis could help bring cholesterol levels even more under control.

Heart disease remains a leading cause of death worldwide, despite advances in cholesterol-lowering medication such as proprotein convertase subtilisin-kexin type 9 inhibitors, which were approved by the FDA in 2015. One clinical trial following patients taking proprotein convertase subtilisin-kexin type 9 inhibitors demonstrated a benefit while also revealing an opportunity for improvement as the absolute risk reduction was considered modest at 1.5%.

“It is clear that there is more going on than just what statins and these newer inhibitor drugs can control,” says Ze Zheng, MBBS, PhD, MCW assistant professor of medicine. “More therapies are needed, and to get them we need to know more about other sources of risk for heart disease, especially heart attacks and strokes.”

So-called “bad cholesterol” is carried by apolipoprotein B (apoB) which forms well-structured particles with lipids and proteins. These particles serve as stable vehicles for transporting lipids such as cholesterol in the bloodstream. These lipid-rich particles mostly include very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). Current cholesterol-lowering reduce mainly LDL levels, which though important to control, is not the only risk factor for heart disease. In fact, the other lipoproteins in the same group as LDL are not reduced by much with available treatments. Dr Zheng and her team are investigating how to reduce levels of other members of this family of lipoproteins, especially VLDL.

“With my background in lipid metabolism, I found myself consistently checking lipid levels even during studies regarding blood clot lysis and how an impairment in the body’s ability to remove blood clots affects the risk of blood vessel blockages,” Dr Zheng adds. “I was just naturally curious about it, and I noticed that a protein I was studying may have an effect on the amount of circulating cholesterol.”

In prior research, Dr Zheng has helped define a new cellular source of this protein, tissue-type plasminogen activator (tPA), and its role in breaking down blood clots and preventing blood vessel blockages. To understand its potential influence on cholesterol levels, her team used a gene-editing technique to stop liver cells from producing tPA in mice prone to blood vessel plaque formation. The scientists found that the mice developed increased lipoprotein-cholesterol in this experiment, and then validated the findings in follow-up studies using human liver cells and a type of rat liver cell known to produce VLDL in a way similar to human liver cells. With these and other experimental results, Dr Zheng and her team have demonstrated a new, important role that liver tPA influences blood cholesterol levels while underscoring a meaningful connection between the liver, heart and blood vessels.

“After defining this new role for tPA, we turned our attention to the question of how it changes blood cholesterol levels,” notes Wen Dai, MD, research scientist, Versiti Blood Research Institute.

The liver contributes to the majority of the “bad” apoB-lipoproteins by making VLDL. The team focused on whether and how tPA impacts the process of VLDL assembly in the liver. Microsomal triglyceride transfer protein (MTP) is required for the assembly of VLDL due to its role carrying lipids to the apoB. The scientists determined that tPA binds with the apoB protein in the same place as MTP. The more tPA is present, the fewer opportunities MTP has to connect with apoB and catalyse the creation of new VLDL. Essentially, MTP tries to pass a cholesterol to apoB, but tPA interferes with this pocess.

“Based on our prior research, we knew it also was critical to look at tPA’s primary inhibitor,” Dr. Zheng says.

Plasminogen activator inhibitor-1 (PAI-1) is known to block the activity of tPA. Scientists also have found a correlation between PAI-1 levels in blood and the development of disease due to plaque formation and blockages in blood vessels. The team found that higher levels of PAI-1 reduced the ability of tPA to bind with apoB proteins, rendering tPA less effective at competing with MTP to prevent VLDL production. Returning to the biological gridiron, PAI-1 might be a decoy receiver that distracts tPA until MTP connects with apoB for a big gain. The team studied this interaction in human subjects with a naturally occurring mutation in the gene carrying the code for PAI-1. The researchers found that these individuals, as predicted, had higher tPA levels and lower LDL and VLDL levels than individuals from the same community who did not have the same mutation.

“We are investigating therapeutic strategies based on these findings regarding tPA, MTP and PAI-1,” Dr Zheng notes. “I think we may be able to reduce the residual cardiovascular risk that has persisted even as treatment has advanced.”

Source: Medical College of Wisconsin

Categories : Neurodegenerative DiseasesTags :

Finding the Right Treatment for Controlling Parkinson’s Symptoms

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Photo by JD Mason on Unsplash

Finding the right medication regimen to treat Parkinson’s disease (PD) is a complex healthcare challenge. Wearable health trackers provide detailed information on patients’ symptoms, but this complex data is difficult to turn into useful treatment insights. Now, new research in the INFORMS journal Management Science shows that combining wearable health tracker data with state-of-the-art algorithms results in promising treatment strategies that could improve PD patients’ outcomes.

“Our model identified a Parkinson’s disease medication strategy: Frequent dosing of a slow-release medication formulation that would benefit almost all patients,” says Matt Baucum of Florida State University, one of the study authors.

“In fact, our model uses wearable sensors to predict that patients would spend almost twice as long each day (82% longer) with well-managed symptoms under our recommended medication strategy, compared with their existing medication regimens.”

The paper suggests the resulting models can offer novel clinical insights and medication strategies that can potentially democratise access to improved care.

“Our research suggests that combining rich data from wearable health trackers with the pattern-discovery capabilities of machine learning can uncover treatment strategies that otherwise might have gone underutilized,” says Anahita Khojandi, study co-author from the University of Tennessee, Knoxville.

“The algorithms we developed can even be used to predict patients who might benefit from more advanced PD therapies, which really highlights their ability to extract the maximum value from wearable data.”

Baucum and Khojandi, alongside fellow authors Dr Rama Vasudevan of Oak Ridge National Laboratory and Dr Ritesh Ramdhani a neurologist at Hofstra/ Northwell, emphasise that this work is ground-breaking for PD patients who may experience improved symptom control through continuous sensor monitoring and a novel AI approach.

Source: Institute for Operations Research and the Management Sciences

Categories : Cardiovascular DiseaseTags :

Brain Haemorrhage Risk Factor could be Transmissible via Blood Transfusion

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A major study led by researchers at Karolinska Institutet suggests that a possible cause of spontaneous brain haemorrhage could be transmitted via blood transfusion. At the same time, it is very unlikely that anyone should suffer a brain haemorrhage after receiving donated blood, according to the study findings which are published in JAMA.

A common cause of spontaneous, recurring brain haemorrhages is the vascular disease cerebral amyloid angiopathy (CAA), in which proteins accumulate along the small blood vessels of the brain. Several studies have shown that CAA can be transferred from one individual to another through neurosurgery and probably via treatment using a certain type of growth hormone.

Few affected individuals

This new study led by researchers from Karolinska Institutet shows that patients who have received blood from donors who later suffered recurring brain haemorrhages are more than twice as likely to suffer a brain haemorrhage themselves.

The findings suggest that some factor that can give rise to spontaneous brain haemorrhages can be spread through blood transfusion. However, as only 0.1% of the donors in the study subsequently suffered recurring brain haemorrhages there were consequently only a few affected patients.

“Blood transfusions are relatively common, which makes possible negative effects an important public health issue,” says the study’s last author Gustaf Edgren, researcher at the Department of Medicine, Karolinska Institutet (Solna) and specialist physician at Södersjukhuset. “However, in this case, it’s very unlikely that you’d suffer a brain haemorrhage from something transmitted through a transfusion.”

CAA could be transmissible

According to the researchers, the most important implication of the study is instead that it adds further support to the hypothesis that CAA can be transmitted between individuals, which, if true, can have consequences in several fields.

The study drew on the data of more than a million patients the Swedish-Danish transfusion database SCANDAT, which contains data on blood donors and patients receiving a transfusion from the 1970s onwards. The primary analyses were conducted in Sweden and then repeated with the Danish data, with almost identical results.

Confirmation needed

The researchers now hope to corroborate the hypothesis that the link between brain haemorrhage and blood transfusion concerns CAA. They will therefore be examining samples from the Danish Blood Donor Study biobank to see if they can identify aberrant proteins associated with the disease.

The plan is also to obtain CAT and MR scans from the affected donors and patients to see if they might also be able to support the hypothesis.

“This study does not demonstrate causality, so the observed increase in risk could depend on other factors,” says the study’s first author Jingcheng Zhao from Dr Edgren’s group at Karolinska Institutet. “More research is needed to confirm our findings and understand the potential underlying mechanism.”

Source: Karolinska Institutet