Tag: 13/9/23

Categories : Cardiovascular Disease Metabolic DisordersTags : Leave a comment

New Research Points to Clot Lysis Protein for Cholesterol Control

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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 : Leave a comment

Finding the Right Treatment for Controlling Parkinson’s Symptoms

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Photo by Kampus Production: https://www.pexels.com/photo/a-man-in-blue-sweater-sitting-beside-man-in-white-long-sleeves-7551646/

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 : Leave a comment

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

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Healthcare Industry Embracing Digital Disruption to Improve Physical Care

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Photo by Tima Miroshnichenko on Pexels

The healthcare industry is in the midst of a digital revolution. We are witnessing a growth in healthcare consumerism, where patients and consumers are more active and engaged, keen to track their own health and are more understanding of their body. Digital therapeutics are emerging and disruptive technologies that overcome the limitations of place, time, and availability of healthcare resources in South Africa.

Digital therapeutics is the key to shifting from reactive healthcare to proactive holistic care. By leveraging technologies such as artificial intelligence/machine learning (AI/ML), augmented reality/virtual reality (AR/VR), m-health applications, and gamified platforms, these software driven intelligent solutions empower patients and healthcare providers with high-quality, safe, and effective data based interventions. 

Christo Groenewald, CEO of CompuGroup Medical South Africa, a MedTech company that has spent over 20 years researching and providing tools doctors, dentists and medical professionals worldwide, has identified two key stages during the interaction between a patient and the healthcare professional, where digital platforms can build a more efficient relationship.    

STEP ONE:  Keeping accurate records

From the first call or appointment, preferably through an online booking system, being able to quickly capture data and access these records saves time and helps gain a deeper understanding of the patient’s experience. This also helps practitioners make informed decisions about the necessary treatment.  

Clinical documentation can effortlessly be facilitated through the employment of systems such as SOAP (subjective, objective, assessment, and plan) or SINSS (severity, irritability, nature, stage, and stability) model, further complemented by user-friendly aids for methodical body chart completion.

Should a referral be necessary, the uniformity of the anatomy chart and notes make it easy for colleagues to understand the consulting history and it can be shared with the patient on request or their medical aid. 

STEP TWO:  Real time imaging

The future of medicine must include integration with diagnostic imaging, which currently often involves multiple departments and hard copies such as x-rays and scans. One digital therapeutics feature that is gaining popularity, especially in sports medicine, is the capacity to visually map pain and musculoskeletal concerns on an interactive 360-degree model of the human body, enhancing diagnostic precision and patient comprehension.

This visual system also helps with virtual consulting, requesting blood work from the labs or writing e-scripts, which is increasingly being done and recorded remotely.

Software programmes, such as Practice Perfect by CGM, are now trusted for their capability to easily capture comprehensive medical and treatment histories right at the point of care. This sleek approach facilitates efficient tracking of patient rehabilitation, fitness progress, and treatment responses. The ability to merge personal and clinical data in real time, paints a portrait of each patient’s physical health, empowering accurate diagnoses, prognosis and subsequent follow-ups. 

Constantly evolving

Top multinational MedTech companies have invested heavily in the development and advancement of their platforms so that they can be used to predict and manage a patient’s future health rather than reacting to symptoms. This will help reduce the disease burden and be a cost saving for insurance providers and private and public health sectors and empower patients to take control of their physical wellbeing. 

Dr Roberto Beffa, a Cape Town based chiropractor states that “As a loyal customer of CGM for more than a decade, I can confidently say that their Perfect Pair solution has truly helped shape my practice. The seamless integration of clinical notes and billing information in one user-friendly platform has transformed our operations, making the flow from clinical documentation to billing a breeze. Thanks to this efficient system, I can now dedicate more time to what I am truly passionate about – providing exceptional care to my patients”.

For more information about CGM’s Perfect Pair, which is a combination of Practice Perfect plus the powerful billing engine for physical health practitioners, CGM MEDEDI, visit www.cgm.com/za.

Categories : GastrointestinalTags : Leave a comment

Turmeric as Effective as Omeprazole for Treating Dyspepsia, Comparative Study Suggests

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A natural compound found in the culinary spice turmeric may be as effective as the proton pump inhibitor (PPI) omeprazole for treating indigestion symptoms, suggests the first study of its kind, published online in the journal BMJ Evidence-Based Medicine.

Turmeric is derived from the root of the Curcuma longa plant. The spice contains a naturally active compound called curcumin thought to have anti-inflammatory and antimicrobial properties, and has long been used as a medicinal remedy, including for the treatment of indigestion, in South East Asia. 

But it’s not clear how well it compares with conventional drugs for this indication, largely because there have been no head to head studies.

The researchers therefore randomly assigned 206 patients aged 18–70 with recurrent upset stomach (functional dyspepsia) of unknown cause, recruited from hospitals in Thailand between 2019 and 2021, to one of three treatment groups for a period of 28 days.

These were: turmeric (two large 250mg capsules of curcumin 4 times a day) and one small dummy capsule; omeprazole (one small 20mg capsule daily and two large dummy capsules 4 times a day; and turmeric plus omeprazole.

PPIs such as omeprazole are used to treat functional dyspepsia, the symptoms of which include postprandial fullness, early satiety, and pain and/or epigastric pain.

But long term use of PPIs has been linked to increased fracture risk, micronutrient deficiencies, and a heightened risk of infections, note the researchers.

Of the 206 patients enrolled, 151 completed the study, with 20 in the curcumin group;19 in the omeprazole group; and 16 in the combined treatment group, dropping out. 

Patients in all three groups had similar clinical characteristics and indigestion scores, as assessed by the Severity of Dyspepsia Assessment score or SODA, at the start of the trial. Patients were reassessed after 28 days and then again after 56 days.

SODA scores indicated significant reductions in symptom severity by day 28 for pain (−4.83, –5.46 and −6.22) and other symptoms (−2.22, –2.32, and −2.31) for those in the combined, curcumin alone, and omeprazole alone groups, respectively. 

These improvements were even stronger after 56 days for pain (−7.19, –8.07 and −8.85, respectively) and other symptoms (−4.09, –4.12 and −3.71, respectively). 

SODA also captures satisfaction scores: these scarcely changed over time among the curcumin users, which might possibly be related to its taste and/or smell, suggest the researchers.

No serious side effects were reported, although liver function tests indicated some level of deterioration among curcumin users carrying excess weight, note the researchers.

They acknowledge the small size of the study, as well as several other limitations, including the short intervention period and lack of long-term monitoring data. Further larger, long term studies are needed, they say.

Nevertheless, they conclude: “This multicentre randomised controlled trial provides highly reliable evidence for the treatment of functional dyspepsia,” adding that “the new findings from our study may justify considering curcumin in clinical practice.”

Source: EurekAlert!