Month: July 2024

Categories : Substance Use VaccinesTags :

New Vaccine may Counter the ‘Zombie Drug’ Xylazine

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Xylazine, only intended for animals, is being added to opioids and cocaine, with deadly effects. Photo by Colin Davis on Unsplash

Xylazine is an FDA-approved sedative and pain reliever for use in animals, but it has severe adverse effects when used in humans. Now, it is now being added illicitly to opioids, like fentanyl and heroin, as well as cocaine – leading to a sharp rise in overdose deaths.

Scripps Research chemical biologists have developed a vaccine to block the effects of xylazine’s toxicity. The vaccine works by training the immune system to attack the drug, which is described in a new paper published in Chemical Communications.

“We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says study senior author Kim D. Janda, PhD, professor of chemistry at Scripps Research. “There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”

The rapid increase in lethal drug overdoses attributed to xylazine combined with fentanyl prompted the White House Office of National Drug Control Policy to declare this combination an emerging threat to the United States. Xylazine intoxication presents similarly to opioid overdose, causing respiratory and central nervous system depression, and it can heighten the effects of opioids. However, naloxone – typically administered to reverse the effects of opioids – does not tackle the impact of xylazine, highlighting the need for effective measures to treat acute toxicity caused by xylazine.

Researchers suspect xylazine works by reducing blood flow to the brain, among other areas of the body. The drug also causes non-healing skin lesions and wounds, often located on the forearms and lower legs, that can require amputation in some cases – giving it the nickname “zombie drug.”

Although no treatment currently exists, targeted vaccines may offer a solution. Antibodies from vaccination can target toxins as well as viruses and bacteria. But sometimes molecules are too small to initiate an immune response, as is the case with xylazine. So, to circumvent this problem, the researchers created a vaccine using a design principle that Janda pioneered, which relies on pairing the drug molecule (called a hapten) with a larger carrier molecule (a protein) and an adjuvant.

In this study, the scientists combined a xylazine hapten with multiple different protein types, to see which combination would create a robust immune response against xylazine. The team tested three vaccine formulations (termed TT, KLH and CRM197, based on the protein involved) to see which vaccine cocktail could help rodents after being challenged with xylazine. One of the three vaccines (TT) significantly increased movement in mice given xylazine after 10 minutes, while two of the three vaccines (TT and KLH) led to an improvement in breathing.

The scientists also examined how these vaccines would limit xylazine blood brain barrier, (BBB) permeation, a filtering mechanism that scrutinizes drug penetration. When xylazine was injected, it immediately crossed into the brain to bind with receptors. Antibodies typically cannot navigate the BBB; however, two of the three vaccines (TT and KLH) showed a strong ability to stop xylazine from reaching its receptors in the brain, limiting its detrimental effects.

A provisional patent has been filed on the research. In the future, his team will build off this work to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously, something that naloxone cannot do.

“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda. “This strategy could make a significant impact on the opioid epidemic.”  

Source: Scripps Research Institute

Categories : ExerciseTags :

Exercise Scientists Come up with a Simple Fix for Shin Splints

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Photo by Andrea Piacquadio on Pexels

Shin splints are a common complaint among runners, especially if they use treadmills. A randomised controlled trial found that four weeks of gait training outdoors, in addition to home exercises often prescribed for shin splints, led to improved running biomechanics even when the runners were using a treadmill. These improvements included decreasing the time the runners’ feet were in contact with the ground or treadmill, a recently identified contributor to shin splints. 

Based on the trial results, the researchers, including UVA Health sports medicine expert David J. Hryvniak, DO, are recommending that clinicians begin including outdoor gait training as part of rehabilitation programs for patients struggling with chronic shin splints.

“This is an important finding for clinicians, as this gives us a tool to use to help these runners,” said Hryvniak, a running medicine specialist who is part of UVA Health’s Runner’s Clinic. “These gait-training cues can be an easy thing to add into a rehab program to help patients improve running mechanics that can underlie many common running injuries.”

Soothing shin splints

Affecting approximately 40% of all runners, shin splints typically begin as tenderness in the lower leg that goes away after exercising. But for regular runners, this pain can worsen and become persistent. In severe cases, shin splints can even lead to stress fractures.

Prior research has found that short courses of outdoor gait training can significantly reduce shin-splint pain for outdoor runners. But experts had been uncertain if these benefits would transfer to the flat, regular surface of treadmill running. That prompted an interdisciplinary team of researchers to launch a randomised trial to find out if outdoor gait training would benefit treadmill users.

The researchers enrolled 17 treadmill runners between ages 18 and 45 who ran at least three times a week and who had been suffering lower leg pain during or after running for at least a month. The volunteers were randomly divided into two groups: One group received four weeks of outdoor gait training and performed commonly prescribed home strengthening exercises, while the other group only performed the home exercises.

During the gait training, participants were provided with “vibrotactile feedback” – meaning they felt a little vibration – when special sensors in their shoes detected their feet were in contact with the ground for too long. This helped them improve their stride and gait to reduce this potential contributor to shin splints.

At the end of the study period, both groups saw strength improvements in their legs. But the gait trainers also had improved running technique, or what the researchers call “favorable adjustments in running gait mechanics.” And, sure enough, these gait improvements were seen during both outdoor runs and treadmill runs. 

That suggests outdoor gait training could be an important new tool to help treadmill users work up a sweat pain-free, the researchers say.

“Shin splints are a very common running injury, especially with those who are new to the sport,” Hryvniak said. “These gait cues are something that have been shown to be an effective tool that patients can use literally ‘on the run.’” 

Source: University of Virginia Health

Categories : Pain Management Surgeries & ProceduresTags :

A Handful of Procedures Account for Large Share of Post-surgical Opioids

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Photo by Towfiqu Barbhuiya on Unsplash

A handful of common surgical procedures account for large shares of all opioids dispensed after surgery in children and adults, according to two studies recently published by researchers at the University of Michigan.

The studies, published this week in Pediatrics and JAMA Network Open, report that the top three procedures for children ages 0–11 account for 59% of opioids dispensed after surgery (tonsillectomies and adenoidectomies 50%, upper extremity fractures 5% and removal of deep implants 4%). Among those ages 12–21, the top three procedures account for about a third of post-surgery opioid prescriptions (tonsillectomies and adenoidectomies 13%, knee arthroscopies 13% and caesarean deliveries 8%).

For adults ages 18–44, C-sections account for the highest share of opioids dispensed post-surgery (19%), followed by hysterectomies (7%) and knee arthroscopies (6%). Among those ages 45-64, four of the top five procedures were orthopaedic procedures, collectively accounting for 27% of total opioid prescriptions dispensed after surgery.

“Our findings suggest that surgical opioid prescribing is highly concentrated among a small group of procedures. Efforts to ensure safe and appropriate surgical opioid prescribing should focus on these procedures,” said Kao-Ping Chua, lead author of the study in Pediatrics, assistant professor at the U-M Medical School and School of Public Health, and co-director of the Research and Data Domain at the U-M Opioid Research Institute.

To conduct the study, the researchers developed an algorithm to identify 1082 major surgical procedures using procedure codes, a medical classification tool used to identify specific surgical, medical or diagnostic interventions. The algorithm was then applied to identify privately and publicly insured children and adults undergoing surgery from Dec. 1, 2020 through Nov. 30, 2021.

The information was organized through a novel system developed by the study team, which allowed them to connect different sets of data that had previously been seen as unrelated. This new method allows for improved comparability and contrast, according to lead investigators.

In addition to determining which procedures accounted for the highest shares of opioids, the researchers also examined the size of opioid prescriptions for each procedure. For many procedures, prescriptions were far larger than the amount patients typically need for a particular procedure.

“Our findings suggest that there are important opportunities to reduce surgical opioid prescribing without compromising pain control,” said Dominic Alessio-Bilowus, lead author of the paper focused on adults published in JAMA Network Open and a medical student at Wayne State University who just completed a research year at U-M.

Source: University of Michigan

Categories : Medical Research & TechnologyTags :

Systematic Biases on Race and Gender at Play in Clinical Trials

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Photo by National Cancer Institute on Unsplash

Randomized controlled trials, or RCTs, are believed to be the best way to study the safety and efficacy of new treatments in clinical research. However, a recent study from Michigan State University found that people of colour and white women are significantly underrepresented in RCTs due to systematic biases. 

The study, published in the Journal of Ethnicity in Substance Abuse, reviewed 18 RCTs conducted over the last 15 years that tested treatments for post-traumatic stress and alcohol use disorder. The researchers found that despite women having double the rates of post-traumatic stress and alcohol use disorder than men, and people of colour having worse chronicity than white people, most participants were white (59.5%) and male (about 78%). 

“Because RCTs are the gold standard for treatment studies and drug trials, we rarely ask the important questions about their limitations and failings,” said Nicole Buchanan, co-author of the study and professor in MSU’s Department of Psychology. “For RCTs to meet their full potential, investigators need to fix barriers to inclusion. Increasing representation in RCTs is not simply an issue for equity, but it is also essential to enhancing the quality of our science and meeting the needs of the public that funds these studies through their hard-earned tax dollars.”

The researchers found that the design and implementation of the randomised controlled trials contributed to the lack of representation of people of colour and women. This happened because trials were conducted in areas where white men were the majority demographic group and study samples almost always reflected the demographic makeup where studies occurred. Additionally, those designing the studies seldom acknowledged race or gender differences, meaning they did not intentionally recruit diverse samples.

Furthermore, the journals publishing these studies did not have regulations requiring sample diversity, equity or inclusion as appropriate to the conditions under investigation.

“Marginalized groups have unique experiences from privileged groups, and when marginalised groups are poorly included in research, we remain in the dark about their experiences, insights, needs and strengths,” said Mallet Reid, co-author of the study and doctoral candidate in MSU’s Department of Psychology. “This means that clinicians and researchers may unknowingly remain ignorant to how to attend to the trauma and addiction challenges facing marginalised groups and may unwittingly perpetuate microaggressions against marginalised groups in clinical settings or fail to meet their needs.”

Source: Michigan State University

Categories : Obstetrics & GynaecologyTags :

Low-dose Aspirin Could Help Prevent Pregnancy Complications Caused by Flu Infections

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Photo by SHVETS production

A world-first study in animals has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. The study, published in Frontiers in Immunology, showed that treatment for preeclampsia could be applied to flu infections – and the results, according to the research team, were very promising. 

Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels.  

Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.   

“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said. 

“This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.” 

The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice. 

Markers of low oxygen to the blood and poor blood vessel development were also evident in the foetuses. 

However, mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival. 

While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy.  

However, the research team recommended pregnant people seek medical advice before taking new medications.  

Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.  

“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said. 

Source: RMIT University

Categories : Cancer NeurologyTags :

Breast Cancer Chemo Disrupts Gut Microbiome and Impacts Cognition

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Photo by Tima Miroshnichenko on Pexels

Chemotherapy is known to cause behavioural side effects, including cognitive decline. Notably, the gut microbiome communicates with the brain to affect behaviour, including cognition. 

“For the first time ever, our Intelligut Study found that the gut microbiome has been implicated in cognitive side effects of chemotherapy in humans,” said senior author Leah Pyter, associate professor of psychiatry and neuroscience at Ohio State University. “The potential connection between the gut and the brain would allow us to create treatments for the gut to treat the brain.”

Study findings are published in the journal Brain, Behavior, and Immunity.

This clinical longitudinal observational study explored whether chemotherapy-induced disruption of the gut microbiome relates to cognitive decline and circulating inflammatory signals. 

Faecal samples, blood and cognitive measures were collected from 77 patients with breast cancer before, during and after chemotherapy.

“We found that patients treated with chemotherapy who showed decreases in cognitive performance also had reductions in the diversity of their gut microbiome,” said Pyter, also a researcher with Ohio State’s Institute for Behavioral Medicine Research and member of the Cancer Control Research Program at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). 

This research builds on Pyter’s prior research in mouse models that found chemotherapy-induced shifts in the gut microbiome cause neurobiological changes and behavioural side effects.  The current study indicates that an association between gut microbiome and cognitive performance exists in humans as well. 

“Side effects of chemotherapy are common and may reduce quality of life, but these side effects can be dismissed as ‘part of chemotherapy’ and therefore overlooked and under-treated,” Pyter said. “We believe that gut microbiome-focused interventions, such as faecal microbial transplantation, may improve behavioural side effects of chemotherapy.” 

OSUCCC—James researchers are also conducting research studies on how the gut microbiome impacts cancer treatment effectiveness and its role in reducing or increasing cancer risk. 

“Chemotherapy is a very important tool for stopping many cancers and side effects should not deter patients who would benefit from this type of therapy from pursuing it, but we know the side effects of some treatment regimens can be quite challenging for patients to complete,” said David Cohn, MD, interim chief executive officer of the OSUCCC – James. “It’s a careful tightrope of walking between effective cancer control and side effect management – and our team is working every day, in the hospital clinics and the lab, to develop ways to manage the side effects of disease treatment with an eye toward quality of life.” 

Source: Ohio State University

Categories : CancerTags :

How Metastatic Cancer Cells Gain a Foothold

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Colourised scanning electron micrograph of a breast cancer cell. Credit: NIH

Metastatic cancer cells, which cause 90% of cancer-related deaths, must overcome numerous hurdles to spread from a primary tumour through the bloodstream. Now, a new study led by investigators from the Mass General Cancer Center has identified a gene whose expression confers a growth advantage to these cells.

Mechanistically, the gene’s expression allows metastatic cancer cells to cause changes to their surrounding environment so that they can grow in new locations in the body. The findings are published in Nature Cell Biology.

“Our results point to potentially novel therapeutic avenues to specifically target metastatic cancer,” said senior author Raul Mostoslavsky, MD, PhD, who is the scientific director of the Krantz Family Center for Cancer Research at the Mass General Cancer Center.

Mostoslavsky and colleagues first compared gene expression patterns in primary versus metastatic tumours in mice with pancreatic cancer or breast cancer. After identifying various genes whose expression increased in metastatic tumour cells, the researchers silenced each gene individually.

In these experiments, silencing the Gstt1 gene had no effect on primary tumour cells from mice, but it stripped metastatic cancer cells of their ability to grow and spread. It also blocked cell growth in two metastatic-derived human pancreatic cancer cell lines.

Gstt1 encodes an enzyme that is a member of a superfamily of proteins involved with protecting cells from toxins, among other functions. Mechanistic studies indicated that the Gstt1 enzyme causes metastatic cancer cells to modify and secrete a protein called fibronectin, which is important for helping cells to attach themselves to the extracellular matrix, a large network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body.

“Gstt1 alters the matrix surrounding the metastatic cells so they can grow in these foreign niches,” said Mostoslavsky. “Our results could lead to new strategies for the treatment of metastatic disease. This would be especially impactful for pancreatic cancer, in which most patients present with metastases when initially diagnosed.”

Source: Massachusetts General Hospital

Categories : Cancer Neurology Surgeries & ProceduresTags :

New Brain Surgery Approach Targets Difficult Tumours at Skull Base

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Source: CC0

Tumours arising in the base of the skull are among the most difficult to remove in neurosurgery. The current treatment method is to perform surgical removal by what is known as the microscopic anterior transpetrosal approach (ATPA). Seeking to lessen the risk of damage and postoperative complications, as the skull base is densely packed with nerves, blood vessels, and other tissues, not to mention the brain stem, an Osaka Metropolitan University medical research team is taking a new approach.

Led by Dr Hiroki Morisako, a lecturer in the Graduate School of Medicine’s Department of Neurosurgery, and its department head Professor Takeo Goto, the team has developed a minimally invasive surgical technique called a purely endoscopic subtemporal keyhole ATPA. The team members write in The Journal of Neurosurgery that this is, to their knowledge, the first time this procedure to remove lesions in the skull base region known as the petrous apex has been described in an article.

Diagram of skin incision and extent of craniotomy. New endoscopic neurosurgery approach does not require a large craniotomy, so the result is a smaller scar. Credit: Osaka Metropolitan University

The endoscopic technique means a smaller area of the skull needs to be surgically opened compared to the microscopic approach, an average of only 11.2 cm² versus 33.9 cm². The risk of damage to the brain is also reduced.

The team performed 10 neurosurgeries using their method from 2022 to 2023 at Osaka Metropolitan University Hospital and compared the results to 13 surgeries using the microscopic ATPA from 2014 to 2021. In terms of operative time, the endoscopic approach reduced it noticeably, from an average of 410.9 minutes to 252.9 minutes. Similarly, blood loss lessened from a mean of 193 ml to 90 ml. The degree of tumour resection (surgical removal) was just as high as the microscopic method, while neurological functions were preserved at a rate equal to or higher than with the conventional approach.

“Comparison of the new endoscopic method and the conventional microscopic method showed no significant difference in tumour resection rate or in the ability to perform daily activities before and after surgery, with the new endoscopic approach resulting in shorter operative times and less blood loss,” Professor Goto stated. “The widespread use of this surgical procedure is expected to improve the treatment results of brain tumours in the base of the skull, not only in Japan but also worldwide.”

Source: Osaka Metropolitan University

Categories : IT in HealthcareTags :

Hacked Healthcare: New KnowBe4 Report Shines a Spotlight on Cybersecurity Crisis in Sector

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Report shows the alarming global rise of cyberattacks on the healthcare sector and the urgent need to prioritise cybersecurity

Photo by Nahel Abdul on Unsplash

KnowBe4 (www.KnowBe4.com), the provider of the world’s largest security awareness training and simulated phishing platform, released its International Healthcare Report. The report takes a closer look at the cybersecurity crisis currently experienced by the healthcare sector, in particular hospital groups, across the world.

Africa was the global region with the highest average number of weekly cyberattacks per organisation in 2023. One in every 19 organisations on the continent experienced an attempted attack every week. Although South Africa’s healthcare sector has managed to avoid a major attack since 2020, the alarming escalation of attacks in other sectors within the country suggests that it’s only a matter of time before the next attack strikes, making it a question of “when” rather than “if”.

Hospitals have become increasingly attractive targets for ransomware attacks due to their comprehensive patient databases, sensitive information, and their interconnectedness between systems and equipment. Moreover, poor security measures have made hospitals vulnerable to cyber threats. When attacked, cybercriminals can potentially take control of entire hospital systems, and gain access not only to patients’ health information but also their financial and insurance data.

Hospitals are severely impacted by cyberattacks (https://apo-opa.co/4csCXH4), which can lead to a reduction in patient care, loss of access to electronic systems, and a reliance on incomplete paper records. This can also result in the cancellation of surgeries, tests, appointments, and, in some cases, even loss of life.

Some shocking facts discussed in the report include:

  • In the first three quarters of 2023, the global healthcare sector experienced a staggering 1,613 cyberattacks per week, nearly four times the global average, and a significant increase from the same period the previous year.
  • The healthcare sector has seen a dramatic surge in cyberattack costs over the past three years, with the average cost of a breach reaching nearly $11 million, more than three times the global average. This makes healthcare the costliest sector for cyberattacks.
  • Ransomware attacks have been the most prevalent type of cyberattack on healthcare organisations, accounting for over 70% of successful attacks in the past two years.
  • The majority of cyberattacks (between 79% and 91%), across sectors, begin with phishing or social engineering tactics, which allow cybercriminals to gain access to accounts or servers.
  • According to KnowBe4’s 2024 Phishing by Industry Benchmarking Report (https://apo-opa.co/4csuiEB), healthcare and pharmaceutical organisations are among the most vulnerable to phishing attacks, with employees in large organisations in the sector having a 51.4% likelihood of falling victim to a phishing email. This means that cybercriminals have a better than 50/50 chance of successfully phishing an employee in the sector.

“The healthcare sector remains a prime target for cybercriminals looking to capitalise on the life-or-death situations hospitals face,” says Stu Sjouwerman, CEO of KnowBe4. “With patient data and critical systems held hostage, many hospitals feel like they are left with no choice but to pay exorbitant ransoms. This vicious cycle can be broken by prioritising comprehensive security awareness training to empower employees and cultivate a positive security culture as a strong defence against phishing and social engineering attacks.”

The report examines the state of cybersecurity in the healthcare sector in North America, Europe, the United Kingdom, Asia-Pacific, Africa, and Latin America. In addition it also highlights some of the most prolific global ransomware attacks that occurred between December 2023 and May 2024, the aftermath thereof and what healthcare organisations can do to protect themselves from cyberattacks.

To download a copy of KnowBe4’s International Healthcare Report, click here (https://apo-opa.co/3xIjjaY).

Categories : Diseases, Syndromes and Conditions Mental HealthTags :

Dengue Linked to Heightened Short- and Long-term Risk of Depression in Taiwan

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New study also uncovers short-term links with sleep disorders

Photo by Ekamelev on Unsplash

Analysis of the medical records of nearly 50 000 people who experienced dengue fever in Taiwan suggests that this disease is associated with elevated short- and long-term risk of depression. Hsin-I Shih and colleagues of National Cheng Kung University and National Health Research Institutes, Taiwan present these findings in the open-access journal PLOS Neglected Tropical Diseases.

People may develop dengue fever after being bitten by a mosquito carrying the dengue virus. Dengue fever can be mild, but it can also progress to life-threatening severity, and some people may have long-term health effects. Prior research has uncovered links between active dengue fever and psychiatric disorders, such as depression and anxiety. However, few studies have examined the long-term risk of such disorders after a dengue infection.

To address this knowledge gap, Shih and colleagues analysed the medical records of 45 334 dengue patients in Taiwan and, for comparison, 226 670 patients who did not experience dengue. Covering the years 2002 to 2015, the researchers examined whether dengue patients were more likely to develop anxiety, depressive disorders, and sleep disorders at various time points after infection. To help account for other factors that could influence mental health, the dengue patients were grouped with demographically similar non-dengue patients for statistical analysis.

The researchers found that the dengue patients had a greater likelihood of developing a depressive order across all timeframes, including less than three months, three to 12 months, and more than 12 months after their infection. Sleep disorders were only elevated within three to 12 months post-infection, and there was no observable elevated risk of anxiety.

Taking a closer look at patients whose dengue was severe enough for them to be hospitalized, the researchers found an elevated risk of anxiety disorders within the first three months of infection, as well as elevated risk of sleep disorders in the first 12 months. This subgroup also had elevated risk of depression across timeframes.

These findings suggest a potential link between dengue fever and subsequent depressive disorder. However, further research is needed to determine whether dengue contributes directly to development of depression, or if the association is due to some indirect mechanism.

The authors add: “This study highlights a significant association between dengue fever and an elevated risk of depression in both the short and long term, underscoring the need for further research into the mental health impacts of dengue infection.”

Provided by PLOS