Month: August 2022

Categories : Cancer Ethics and LawTags :

Towards Larger, More Representative Lung Cancer Clinical Trials

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Source: NCI

Filling clinical trials and enrolling sufficiently diverse, representative groups of patients, has long been a challenge, partly due to stringent participation guidelines. In an effort to attain larger and more diverse trial groups, an international team of researchers and policymakers has written new recommendations on how to determine eligibility criteria for lung cancer clinical trials.

The group was led in part by David Gerber, MD, along with representatives from the Food and Drug Administration (FDA), National Cancer Institute, European Medicines Agency, pharmaceutical companies, and the LUNGevity Foundation.

The recommendations, published today in JAMA Oncology, offer the first publicly available outline of upcoming FDA draft guidance on lung cancer clinical trials that are expected to make it easier to include more patients.

“This paper is the public’s first look at the FDA’s proposed changes to how we determine who can participate in a lung cancer clinical trial,” said Professor Gerber in the Hematology/Oncology Division at UTSW. “If these changes are successful, they could make clinical trials for lung cancer as well as other cancers more powerful and more representative.”

Ensuring that people from diverse backgrounds join clinical trials is key to properly evaluating how a new treatment will work among patients of all races and ethnicities. But today, only about 5% of all cancer patients enrol in a clinical trial, and only 11% of cancer clinical trial participants identify as a racial or ethnic minority.

For patients with cancer, participation in clinical trials requires not just a decision to try an experimental treatment, but time and energy spent understanding the trial, enrolling in it, and often attending extra testing or clinic appointments. Many researchers agree that complicated, inconsistent, poorly explained, and overly strict eligibility requirements to join a cancer clinical trial exacerbate this problem and are a key reason for the low number of underrepresented minorities in clinical trials.

“So many clinical trials never finish enrollment, close prematurely, or don’t recruit a population that lets researchers generalise the results,” Dr. Gerber said. “I think there’s widespread recognition that eligibility criteria have become too stringent.”

Addressing this for one cancer subtype, advanced non-small cell lung cancer (NSCLC), – the LUNGevity Foundation convened a roundtable discussion with experts from academia, industry, and regulatory bodies. The team assembled a prioritised list of eligibility categories that should be included in the descriptions of all NSCLC clinical trials and recommended criteria for each category. Some suggestions were more lenient than what has typically been included in previous NSCLC trial eligibility criteria; for instance, the team recommended that most patients with prior or concurrent cancers, most patients with brain metastases, and most patients with mild liver impairment – all of whom would likely have been excluded in the past – still be included in trials.

The team also suggested that these categories be clearly laid out on public websites advertising clinical trials in an easily searchable format.

The FDA will be releasing draft guidance on NSCLC clinical trials in the near future and hold a public comment period before finalising them. Other interdisciplinary teams have already convened to standardise eligibility requirements for clinical trials of other cancer types.

If the new guidelines prove effective, Prof Gerber said that clinical trials will likely be easier to fill and provide more complete and timely data on new cancer interventions.

“If you can involve more patients in clinical trials, you’re more likely to complete those trials quickly. That’s going to lead to new treatments faster,” he said.

Source: UT Southwestern Medical Center

Categories : Addiction Mental HealthTags :

Mouse Study Examines the Possible Addiction Risks of Ketamine

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Mouse
Photo by Kanasi on Unsplash

The commonly used anaesthetic ketamine, which is also increasingly prescribed for the relief of depression symptoms, has created concern over whether it poses an addiction risk.

University of Geneva (UNIGE) researchers found that ketamine triggers an increase in dopamine in mice’s brains, and that it also inhibits a specific receptor that precludes the progression to addiction. These results can be found in the journal Nature.

For the past ten years or so, ketamine has also been prescribed to treat the depressive symptoms of people who are resistant to conventional treatments. Its action has the advantage of a swift onset, acting within hours of the first dose, whereas traditional antidepressants take several weeks to act. Although its prescription is increasing for this type of treatment, this substance is still widely debated within the scientific community.

”Some people believe that ketamine presents a strong addictive risk if taken for a long time, others do not. The whole point of our research was to try to provide some answers,” explained Professor Christian Lüscher.

Brief reward system stimulation
The UNIGE researchers allowed mice to self-administer doses of ketamine. ”The drugs intensely stimulate the reward system in the brain, which leads to an increase in dopamine levels. The first step was to observe whether this mechanism was also at work when taking ketamine,” explained Yue Li, a Postdoctoral Scholar in the Department of Basic Neuroscience at the UNIGE Faculty of Medicine.

The scientists found that dopamine levels increased with each dose and induced a positive reinforcement in the mice, which motivated them to repeat the self-administration. ”However, unlike cocaine, for example, we found that the dopamine level fell very quickly after taking the drug,” said Dr Li.

A drug that leaves no ‘mark’
Probing the mechanism behind this phenomenon, the researchers discovered that ketamine triggered an increase in dopamine by inhibiting a molecule called NMDA receptor in the reward centre of the rodent brain. Dopamine then binds to another receptor (called the D2 receptor), which acts as a rapid brake on the increase in dopamine. The researchers also confirmed that the action of the NMDA receptor is necessary to modify the communication between the nerve cells that underlie the behavioural change leading to addiction. Ketamine’s inhibition of the NMDA receptor makes this modification impossible.

”The consequence of this dual action of ketamine is that it does not induce the synaptic plasticity that addictive drugs do and that persists in the brain after the substance has worn off. It is this memorization of the product in the reward system – absent in the case of ketamine – that drives the repetition of consumption,” explained Prof Lüscher. “Therefore, the addictive risk of ketamine appears to be zero in rodents. Is this also the case in humans? Could this risk vary according to the individual? Our study provides a solid framework for debating access to its therapeutic use,” concludes Christian Lüscher.

Source: Université de Genève

Categories : Metabolic Disorders PaediatricsTags :

Dulaglutide Achieves Glycaemic Control in Diabetic Youths

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Photo by Towfiqu Barbhuiya on Unsplash

A trial testing dulaglutide in children and adolescents with diabetes found that it was effective in achieving glycaemic control. The findings, reported in the New England Journal of Medicine, suggest that dulaglutide may be a more convenient pharmacological treatment for youths.

The incidence of type 2 diabetes mellitus is increasing among youths, and metformin has shown high treatment failure against a backdrop of greater insulin resistance and deterioration in β-cell function than in adults. Daily liraglutide and weekly exenatide, glucagon-like peptide-1 receptor agonists, are available, but have complicated administration and exenatide is available only at a single dose level, making it harder to escalate glycaemic control. The researchers sought to determine whether once-weekly treatment with dulaglutide was effective with regard to glycaemic control in youths with type 2 diabetes.

In a double-blind, placebo-controlled, 26-week trial, 154 participants (aged 10–17; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, were randomised in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75mg.

At 26 weeks, the mean glycated haemoglobin level had increased in the placebo group (0.6%) and had decreased in the dulaglutide groups compared to placebo (–0.6% in the 0.75mg group and −0.9% in the 1.5mg group). At 26 weeks, a significantly higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated haemoglobin level of less than 7.0% (51% vs 14%), which was a secondary endpoint. The fasting glucose concentration increased in the placebo group (17.1mg/dL) and decreased in the pooled dulaglutide groups (−18.9mg/dL), and BMI did not change between groups. More gastrointestinal adverse events were reported in dulaglutide therapy than with placebo, and dulaglutide’s safety profile was consistent with that reported in adults.

Overall, the researchers concluded that dulaglutide at a once-weekly dose of 0.75mg or 1.5mg was superior to placebo in improving glycaemic control through 26 weeks among youths with type 2 diabetes (with or without metformin or basal insulin), without an effect on BMI.

Categories : NeurologyTags :

Smartphone Use may Help with Memory Skills

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Photo by Priscilla du Preez on Unsplash

Instead of causing people to become lazy or forgetful, the use of smartphones and other digital devices could help improve memory skills, report the authors of a new study published in Journal of Experimental Psychology: General.

The research, showed that digital devices serve to aid people storing and recalling crucial information. This, in turn, frees up their memory to remember additional, less important, things.

Neuroscientists have previously expressed concerns that the overuse of technology could result in the breakdown of cognitive abilities and cause ‘digital dementia’.

The findings show that, on the contrary, using a digital device as external memory not only helps people to remember the information saved into the device, but it also helps them to remember unsaved information too.

To demonstrate this, researchers developed a memory task to be played on a touchscreen digital tablet or computer. The test was undertaken by 158 volunteers aged between 18 and 71.

Participants were shown up to 12 numbered circles on the screen, and had to remember to drag some of these to the left and some to the right. The number of circles that they remembered to drag to the correct side determined their pay at the end of the experiment. One side was designated “high value,” meaning that remembering to drag a circle to this side was worth 10 times as much money as remembering to drag a circle to the other “low value” side.

Participants performed this task 16 times. They had to use their own memory to remember on half of the trials and they were allowed to set reminders on the digital device for the other half.

The results found that participants tended to use the digital devices to store the details of the high-value circles. And, when they did so, their memory for those circles was improved by 18%. Their memory for low-value circles was also improved by 27%, even in people who had never set any reminders for low-value circles.

However, results also showed a potential cost to using reminders. When they were taken away, the participants remembered the low-value circles better than the high-value ones, showing that they had entrusted the high-value circles to their devices and then forgotten about them.

Senior author Dr Sam Gilbert said, “We wanted to explore how storing information in a digital device could influence memory abilities.

“We found that when people were allowed to use an external memory, the device helped them to remember the information they had saved into it. This was hardly surprising, but we also found that the device improved people’s memory for unsaved information as well.

“This was because using the device shifted the way that people used their memory to store high-importance versus low-importance information. When people had to remember by themselves, they used their memory capacity to remember the most important information. But when they could use the device, they saved high-importance information into the device and used their own memory for less important information instead.

“The results show that external memory tools work. Far from causing ‘digital dementia,’ using an external memory device can even improve our memory for information that we never saved. But we need to be careful that we back up the most important information. Otherwise, if a memory tool fails, we could be left with nothing but lower-importance information in our own memory.”

Source: University College London

Categories : Diseases, Syndromes and ConditionsTags :

What Antivirals are Suitable for Monkeypox Treatment?

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Colourised transmission electron micrograph of monkeypox virus particles (green) cultivated and purified from cell culture. Credit: NIAID

In light of the recent spread of monkeypox virus, now declared a public health emergency of international concern by the World Health Organization, there is a need for treatments. In an article published in Clinical Infectious Diseases, authors review three antiviral agents with activity against monkeypox: cidofovir, brincidofovir, and tecovirimat.

Human monkeypox, caused by the monkeypox virus, a member of the genus Orthopoxvirus within the Poxviridae family of double-stranded DNA (dsDNA) viruses, was first described in a baby in the Democratic Republic of Congo in 1970. Since then, it has resulted in multiple outbreaks in Central and West Africa, and occasionally in Europe and North America. Human-to-human transmission in households has been reported, especially among those unvaccinated against smallpox.

Cidofovir
Although cidofovir has broad activity against many DNA viruses including orthopoxviruses, it is only FDA approved for the treatment of cytomegalovirus retinitis. Cidofovir (CDV) is a prodrug, which must first enter host cells, where it is converted into the active form, CDV diphosphate (CDV-pp). CDV-pp has a prolonged intracellular half-life, and slows viral DNA replication by being incorporated into the growing DNA strand. Pharmokinetics suggest poor oral absorption and is available as intravenous infusions.

In humans, CDV has been used to treat ocular cowpox and as a topical treatment for molluscum cantiogosum.

Brincidofovir
Brincidofovir (BCV) is a lipid-conjugated CDV analogue, FDA-approved in 2021 for the treatment of smallpox. Like CDV, BCV has broad activity against dsDNA viruses. It can be be taken up by the small intestines, and unlike CDV, which slowly crosses cellular membranes, brincidofovir readily enters host cells due to its lipophilicity. Inside cells, BCV is converted into CDV and then CDV-pp. CDV-pp reaches higher intracellular concentrations after BCV administration due to its ability to cross cellular membranes more efficiently. Like CDV, BCV has a prolonged intracellular half-life and inhibits viral replication.

In prairie dog models, which exhibit similarity to the human course, BCV improved survival when administered shortly after infection, suggesting that early treatment is important.

Tecovirimat
Tecovirimat was FDA approved in 2018 for the treatment of smallpox, and has activity against orthopoxviruses, but has no notable activity against other dsDNA viruses. Tecovirimat targets a gene which encodes for membrane protein p37, responsible for the formation of extracellular enveloped virus.

The oral route results in better absorption for tecovirimat, and is effective against monkeypox virus in macaques and prairie dogs. Administration within 72 hours of exposure to poxvirus reduced lesion severity and mortality in various animal models.

Tecovirimat synergises with BCV, and was successfully used to treat monkeypox in two human cases.

Conclusion
The authors note that while CDV and BCV inhibit DNA replication, tecovirimat is more specific to orthopoxviruses and prevents enveloped virus formation, stalling cell-cell transmission.

BCV and tecovirimat could be promising therapeutic candidates based on their tolerability profiles, they conclude. More studies are needed to identify those most at risk from monkeypox and establish the optimal initiation time and duration for therapy.

Categories : UncategorizedTags :

Hyaluronic Acid Wakes up Stem Cells to Repair Muscles

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Credit: Dr Kiran Nakka

A new study published in the journal Science reveals a unique form of cell communication that controls muscle repair, coordinated by hyaluronic acid. In damaged muscle, stem cells must work together with immune cells to complete the repair process, yet how these cells coordinate to ensure the efficient removal of dead tissue before making new muscle fibres has remained unknown.

“When muscles get damaged, it is important for immune cells to quickly enter the tissue and remove the damage before stem cells begin repair,” said Dr Jeffrey Dilworth, senior author on the study. “Our study shows that muscle stem cells are primed to start repair right away, but the immune cells maintain the stem cells in a resting state while they finish the cleanup job. After about 40 hours, once the cleanup job is finished, an internal alarm goes off in the muscle stem cells that allows them to wake up and start repair.”

Dr Dilworth and his team identified hyaluronic acid as the key ingredient in this internal alarm clock that rouses muscle stem cells from their slumber. When muscle damage occurs, stem cells start producing and coating themselves with hyaluronic acid, which, when thick enough, blocks the sleep signal from the immune cells, thereby causing the muscle stem cells to wake up.

Using mouse and human tissues, the researchers also discovered how muscle stem cells control the production of hyaluronic acid using epigenetic marks on the Has2 gene.

“Interestingly, ageing is associated with chronic inflammation, muscle weakness and a reduced ability of muscle stem cells to wake up and repair damage,” said lead author Dr Kiran Nakka. “If we could find a way to enhance hyaluronic acid production in the muscle stem cells of older people it might help with muscle repair.”

The regenerative effect of hyaluronic acid seems to depend on it being produced by the muscle stem cells, the authors noted. They are currently investigating if drugs could epigenetically stimulate muscle stem cells to increase their production of hyaluronic acid.

Categories : NeurologyTags :

Why do We Struggle to Recognise the Faces of People of Other Races?

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An Asian man and two white men enjoying St. Patrick’s Day Photo by Pressmaster on Pexels

In a study published in Scientific Reports, cognitive psychologists at the believe they have discovered the answer to a 60-year-old question as to why people find it more difficult to recognise faces from visually distinct racial backgrounds than they do their own.

This phenomenon named the Other-Race Effect (ORE) was first discovered in the 1960s. Humans seem to use a variety of markers to recognise people, instead of photographically memorising their faces, which may be based on what they observe in others around them. Hair and eye colour may be used by white people to tell apart other white people since those features vary considerably in that racial group. Setting may also be important: some people might not notice that the centre man in the picture above is Asian while his friends on either side are white.

The ORE has consistently been demonstrated through the Face Inversion Effect (FIE) paradigm, where people are tested with pictures of faces presented in their usual upright orientation and inverted upside down. Such experiments have consistently shown that the FIE is larger when individuals are presented with faces from their own race as opposed to faces from other races.

The findings spurred decades of debate, and social scientists took the view that indicates less motivation for people to engage with people of other races, making a weaker memory for them. Cognitive scientists posited it is down to a lack of visual experience of other-race individuals, resulting in less perceptual expertise with other-race faces.

Now, a team in the Department of Psychology at Exeter, using direct electrical current brain stimulation, has found that the ORE would appear to be caused by a lack of cognitive visual expertise and not by social bias.

“For many years, we have debated the underpinning causes of ORE,” said Dr Ciro Civile, the projects lead researcher.

“One of the prevailing views is that it is predicated upon social motivational factors, particularly for those observers with more prejudiced racial attitudes. This report, a culmination of six years of funded research by the European Union and UK Research and Innovation, shows that when you systematically impair a person’s perceptual expertise through the application of brain stimulation, their ability to recognise faces is broadly consistent regardless of the ethnicity of that face.”

The research was conducted at the University of Exeter’s Washington Singer Laboratories, using non-invasive transcranial Direct Current Stimulation (tDCS) specifically designed to interfere with the ability to recognise upright faces. This was applied to the participants’ dorsolateral prefrontal cortex, via a pair of sponges attached to their scalp.

The team studied the responses of nearly 100 White European students to FIE tests, splitting them equally into active stimulation and sham/control groups. The first cohort received 10 minutes of tDCS while performing the face recognition task involving upright and inverted Western Caucasian and East Asian (Chinese, Japanese, Korean) faces. The second group, meanwhile, performed the same task while experiencing 30 seconds of stimulation, randomly administered throughout the 10 minutes – a level insufficient to induce any performance change.

In the control group, the size of the FIE for own-race faces was found to be almost three times larger than the one found for other-race faces confirming the robust ORE. This was mainly driven by participants showing a much better performance at recognising own-race faces in the upright orientation, compared to other-race faces – almost twice as likely to correctly identify that they had seen the face before.

In the active tDCS group, the stimulation successfully removed the perceptual expertise component for upright own-race faces and resulted in no difference being found between the size of the FIE for own versus other-race faces. And when it came to recognising faces that had been inverted, the results were roughly equal for both groups for both races, supporting the fact that people have no expertise whatsoever at seeing faces presented upside down.

“Establishing that the Other-Race Effect, as indexed by the Face Inversion Effect, is due to expertise rather than racial prejudice will help future researchers to refine what cognitive measures should and should not be used to investigate important social issues,” said Ian McLaren, Professor of Cognitive Psychology. “Our tDCS procedure developed here at Exeter can now be used to test all those situations where the debate regarding a specific phenomenon involves perceptual expertise.”

Source: University of Exeter

Categories : Diseases, Syndromes and ConditionsTags :

HSV-1 Driven by Ancient Migrations – and Introduction of Kissing

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Photo by Cottonbro on Pexels

The HSV-1 virus strain behind facial herpes, commonly known as cold sores, emerged approximately 5000 years ago, according to University of Cambridge-led research published in Science Advances. The virus arose in the wake of vast Bronze Age migrations into Europe from the Steppe grasslands of Eurasia, and associated population booms that boosted transmission.

Two-thirds of the world’s population below the age of 50 now carry HSV-1, manifesting as occasional lip sores. In combination with other ailments – sepsis or even COVID, for example – the virus can be fatal. In 2018, two women died of HSV-1 infection in the UK following Caesarean births.

Herpes has an ancestry dating back millions of years, infecting species from bats to coral. Despite being prevalent among humans today, however, scientists say that ancient examples of HSV-1 were surprisingly hard to find.

According to the study authors of the study, , the Neolithic flourishing of facial herpes detected in the ancient DNA may have coincided with the advent of a new cultural practice imported from the east: romantic and sexual kissing.    

“Facial herpes hides in its host for life and only transmits through oral contact, so mutations occur slowly over centuries and millennia,” said Dr Charlotte Houldcroft, co-senior author.

“We need to do deep time investigations to understand how DNA viruses like this evolve. Previously, genetic data for herpes only went back to 1925.”

The team managed to hunt down herpes in the remains of four individuals stretching over a thousand-year period, and extract viral DNA from the roots of teeth. Herpes often flares up with mouth infections: at least two of the ancient cadavers had gum disease and a third smoked tobacco.

The oldest sample came from an adult male excavated in Russia’s Ural Mountain region, dating from the late Iron Age around 1500 years ago.

Two further samples were local to Cambridge, UK. One a female from an early Anglo-Saxon cemetery a few miles south of the city, dating from 6-7th centuries CE. The other was a young adult male from the late 14th century who had suffered appalling dental abscesses. 

The final sample came from a young adult male excavated in Holland: a fervent clay pipe smoker, most likely massacred by a French attack on his village by the banks of the Rhine in 1672. 

“We screened ancient DNA samples from around 3000 archaeological finds and got just four herpes hits,” said co-lead author Dr Meriam Guellil, from Tartu University’s Institute of Genomics.

“By comparing ancient DNA with herpes samples from the 20th century, we were able to analyse the differences and estimate a mutation rate, and consequently a timeline for virus evolution,” said co-lead author Dr Lucy van Dorp, from the UCL Genetics Institute.     

Co-senior author Dr Christiana Scheib said: “Every primate species has a form of herpes, so we assume it has been with us since our own species left Africa.”

“However, something happened around five thousand years ago that allowed one strain of herpes to overtake all others, possibly an increase in transmissions, which could have been linked to kissing.”

The first known report of kissing is a Bronze Age manuscript from South Asia, and suggest the custom, not found in most human cultures, may have travelled westward with migrations into Europe from Eurasia.   

In fact, centuries later, the Roman Emperor Tiberius tried to ban kissing at official functions to prevent disease spread, a decree that may have been herpes-related.

However, for most of human prehistory, HSV-1 transmission would have been ‘vertical’: passing from infected mother to newborn child.

Source: University of Cambridge

Categories : GastrointestinalTags :

Gold Nanoparticles Ease IBD Inflammatory Symptoms

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Gold bars
Photo by Jingming Pan on Unsplash

In a Chinese study published in Fundamental Research, researchers explored a treatment for inflammatory bowel disease (IBD) using ultrasmall gold nanoparticles. Previous studies showed that these nanoclusters effectively eliminate a variety of reactive oxygen species (ROS), elevated levels of which are commonly found in the gastrointestinal tract of IBD patients.

IBD includes ulcerative colitis and Crohn’s disease, both of which tend to be debilitating, lifelong conditions that can prove fatal in severe cases. Currently, there is no cure for IBD. The main clinical treatments are drugs such as aminosalicylic acid preparations and corticosteroids, but they are often accompanied by gastrointestinal problems, anaemia, and various intestinal complications. Finding alternative, more effective options is a priority for researchers.

The team found that administering gold (Au25) nanoclusters orally to mice suffering from colitis eliminated ROS, increased antioxidant enzymes, and inhibited pro-inflammatory cytokines, without any obvious side effects. According to paper author Fei Wang of China’s The Seventh Affiliated Hospital of Sun Yat-Sen University, a reduction in the inflammation in the gastrointestinal tracts of the mice was observed within 24 hours. She added: “And the fact that these nanoclusters can be administered orally, means there is no need for invasive procedures.”

Additionally, the team found that the nanoclusters have a number of benefits when compared with natural enzymes used in traditional IBD treatments, including lower cost, better stability, mass synthesis and easier storage. Wang explained: “The storage of Au25 nanoclusters was not affected by pH, temperature or solution medium, and their good physiological stability and acid resistance meant they were easily able to access the inflamed colon. They also have good biocompatibility and chemical stability and can remove a variety of ROS.”

Wang concluded: “Au25 nanoclusters offer a promising strategy in the research field of nanomedicine therapy for IBD. We believe this study demonstrates their value as a scientific basis and experimental basis for the clinical treatment of IBD.”

Source: EurekAlert!

Categories : Hospitals Medical IndustryTags :

Mediclinic Agrees to £3.7bn Buyout by Remgro Consortium

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After turning down a previous bid, Mediclinic has agreed to a £3.7 billion buyout by a consortium consisting of investment group Remgro Limited and Mediterranean Shipping Company (MSC).

The buyout will give Remgro and MSC, through a jointly owned subsidiary, a 50/50 stake in the healthcare company.

The offer still has to be cleared by 75% of Mediclinic’s shareholders (Remgro is already a shareholder), but according to the The Daily Maverick, Mediclinic’s CFO, Gert Hattingh, the company’s directors consider the terms of the sale to be fair and reasonable. In addition, regulatory approval must be granted in South Africa, Namibia, Switzerland and Cyprus for the acquisition to proceed.

The current bid is offering 504 pence per share, a 35% increase on the first rejected offer, according to MoneyWeb. With the £3.7 billion buyout, Mediclinic has an implied enterprise value of roughly £6.1 billion.

Mediclinic operates 74 hospitals as of March this year, with 50 hospitals in Southern Africa (three of which are in Namibia), 17 hospitals in Switzerland, seven in the UAE and a 200-bed hospital due to open in Saudi Arabia.

The 72-year-old Johann Rupert who leads Remgro and has a 7% ownership, is South Africa’s richest person, with a personal fortune of $8.8bn, according to the most recent estimate by Forbes.

Commenting on the acquisition, Dame Inga Beale, Chair of Mediclinic, said: “The recommended offer represents a near-term value realisation for Mediclinic shareholders at an attractive premium.

“Over 39 years, Mediclinic has developed into the leading international healthcare services group it is today. During this time, Remgro has remained a supportive long-term shareholder. Together with SAS, the Consortium’s resources will put Mediclinic in a strong position to continue to serve patients through our broad range of high-quality healthcare services.”