Month: November 2020

Questions Raised over Oxford’s Unusual Vaccine Regimen

The recent announcement of the Oxford’s and AstraZeneca’s vaccine trial being 70% effective up to 90% effective has raised some pointed questions.

The trial had two treatment arms, one receiving two full doses of the AZD1222 vaccine and a half dose plus a full dose, with the doses being administered 28 days apart. The “half dose then full dose”  treatment arm reported the 90% protection. The problem was that the trial was never meant to have such an arm. 

It was noticed that some participants were only receiving a half dose because they were experiencing fewer effects than expected such as arm pain and headache. This was subsequently corrected so that they would still receive the full dose on the second administration.

Of particular concern is that the “90% effectiveness” is based on a much smaller subset of the trial participants, with a correspondingly higher statistical uncertainty. So much so that there is statistical overlap with their lower effectiveness of 62% quoted for the two full doses. Furthermore, the participants were from the initial stages of the vaccine trial, where they were aged 18-55 and therefore have little applicability to the results of the main trial which included older age groups as well. 

The details of exactly why the half-measure doses came to be administered in the first place have not been revealed by Oxford or AstraZeneca. Meanwhile in the US, a Phase III of the trial is being rolled out with 40 000 participants, and the “half dose then full dose” regimen may be included – however, uncertainty about it and whether it isn’t a statistical fluke will have to be cleared up first.

Source: Ars Technica

Simple New Method to Improve Time Release of Drugs

Researchers have developed a new method to measure the release of drugs over time, using a simple method.

OxyContin, containing the opiate oxycodone, was intended to offer 12-hour pain relief. Instead, in some patients it dissolved much more quickly, causing them to take it more frequently and ultimately become addicted. But assessing how a drug dissolves in the body is surprisingly tricky. Drug dissolution has to be measured under laboratory conditions that come as close as possible to mimicking what happens in the body.

Corresponding author William Grover, associate professor of bioengineering at the Marlan and Rosemary Bourns College of Engineering explains: “We directly measured dissolution profiles of single drug granules, which are the little spheres you see when you open up a capsule. We accomplished this using a vibrating tube sensor, which is just a piece of glass tubing bent in the shape of a tuning fork.”

Many factors influence the way a drug is dissolved in the body, such as the chemical composition and pH of the fluid, the patient’s sex and their metabolism. Meals taken also have a strong impact: taking a fatty meal increases the amount of oxycodone released from OxyContin by 25%.

Pharmaceutical companies simulate these conditions in test vessels to build a profile of how the drug works over time, but this has its drawbacks. The position of tablets in the vessels can affect dissolution rates; equipment can become clogged; the process is very time-consuming and they only provide brief snapshots over time.

The new approach takes a radically different approach, measuring the mass of a drug granule as it dissolves. This is accomplished by changes in the resonant frequency, which can be measured over time instead of being sampled.

Using the technique on three proton-pump inhibitors, the researchers found considerable variations between name-brand and generic formulations of the drugs, affecting the rate at which the drugs are absorbed by patients.

“Our technique is much cheaper and easier to perform than conventional methods, and that enables pharmaceutical companies to do more tests in a wider variety of conditions,” said Grover. “We can also easily see differences in dissolution between individual particles in a drug. That should help pharmaceutical companies improve and monitor the consistency of their manufacturing processes.”

Source: Medical Xpress

AI Solutions Are No Magic Bullet Against COVID

A leading researcher in the field of medical image analysis has cautioned against the rush to provide AI solutions to the COVID pandemic, arguing that the need to help out must not compromise scientific principles.

Prof Hamid Tizhoosh, head of KIMIA Lab, Faculty of Engineering at the University of Waterloo wrote a piece on Medical-News.Net where he laid out the problems involved in such “quick fix” solutions.

He explains that AI researchers often make “toy” datasets which they use to experiment with in their own labs. In the middle of the pandemic, it is difficult to collaborate with radiographers who have their hands full dealing with COVID patients’ images.

AI research requires the acquisition and curation of large amounts of high-quality data, and currently there is an absence of this. While there are still few publicly available X-ray images or CT images of COVID patients’ lungs, they are beginning to crop up on the internet. AI researchers and enthusiasts are scraping together these images for their data sets and supplementing them with those of pneumonia patients, which are much more readily available. The results of their AI work are being released in papers that are not peer reviewed, yet some claim to be authoritative solutions.

Tizhoosh draws attention to the validity of this data. In one instance, he saw that the data included a pneumonia case from a paediatric patient. He cautions that, “AI is neither a ventilator nor a vaccine nor a pill; it is extremely unlikely that the exhausted radiologists in Wuhan, Qom or Bergamo download the Python code of our poorly trained network (using insufficient and improper data and described in quickly written papers and blogs) to just obtain a flawed second opinion.”

He concludes that the AI developments must come after appropriate images are made available by hospitals, that ethics approval is received and the data is properly de-identified.

Netcare CEO Recounts Challenges and Lessons of 2020

In an interview posted on Moneyweb, the CEO of Netcare, Dr Richard Friedland, related how the company had weathered a very hard financial year.

“We have certainly felt the effects financially and we haven’t been able to pay a dividend to shareholders. But, as I’ve said to all of our frontline workers, we paid a dividend to South Africa in terms of looking after so many thousands – more than 28 000 Covid patients. That is far more significant than anything we could have done in monetary terms,” said Friedland.

The company learned valuable lessons, being at “the tip of the spear” of the COVID pandemic. Following their first cases on March 9, a large outbreak occurred at St Augustine’s, followed by a much smaller one at Kingsway. 

Friedland spoke of the sacrifices the staff had made over the past months, saying “This is not a time to abandon them. It’s a time to stand with them. It does mean our recovery will be longer, but we’ll do that together. And I think it’s critically important, given the headwinds we’re facing in South Africa.”

The company made much of its profit from asset disposal, but Friedland said that they were seeing a return to demands for elective surgery, excepting their two hospitals in the Nelson Mandela Bay area. He noted that there was a noticeable uptick in cases, similar to what they had experienced in the first wave, and that their hospitals were relatively full. However, they were putting their lessons learned into practice by having readied adequate stores of PPE and oxygen, for example. The length of stay has been reduced from 22 days to seven. He remarked on how stressful the pandemic had been for all concerned, but he said that continued efforts must be made.

“[…]Covid nearly robbed us of our humanity, and we need to be very careful about that going forward, particularly as healthcare workers, when patients cannot see their loved ones, when they’ve got to communicate with us through masks and spaces. We’ve managed to find other ways, through Facetime and mobiles, to communicate with their loved ones; but there’s no excuse for [not] improving communication all the time. I think Covid exposed that and there’s been a lot of anxiety as a result that we still need to manage,” concluded Friedland.

Cash for Medical Intern Posts to be Investigated

The South African Medical Association (Sama) has said that it will investigate claims that changes of intern position at hospitals are being sold for cash.

On Monday, Sama chair Dr Angelique Coetzee said that this violated doctors’ ethical responsibility to provide treatment to patients regardless of whether that location suited the doctor or not.

Students were reportedly prepared to pay up to R100 000 for posts at their hospital of choice.

“We simply cannot have a situation where intern positions are being ‘sold’ for whatever reason. The placement of interns is a difficult process, and many doctors are unfortunately not placed where they want to be. For those fortunate enough to have found placements, to now sell them to the highest bidders is not fair on others waiting for legitimate placements,” Coetzee said.

The trading of posts reportedly takes place over social media platforms and messaging services, including Facebook and Telegram.

“Given the complexities and historical issues with the placement of intern doctors, the current haggling over preferred placements is out of touch with the realities of the situation. And, ultimately, this sends the message that with enough money, certain people are able to buy themselves the placements of their choice, a situation we cannot accept or tolerate,”  Coetzee said.

Source: Sowetan Live

Cutting Edge Bio-printing Fabricates Tiny Kidneys

Researchers from the Murdoch Children’s Research Institute (MCRI) and biotech company Organovo have successfully bio-printed miniature human kidneys with unparalleled speed and quality to be used for toxicity screening of medications known to cause kidney damage. 

A world leader in modeling the kidney, Professor Melissa Little of the MRCI said, “Drug-induced injury to the kidney is a major side effect and difficult to predict using animal studies. Bioprinting human kidneys are a practical approach to testing for toxicity before use.”

The new study involved testing the toxicity of aminoglycosides, a class of antibiotics that commonly damage the kidney. The study revealed deaths of certain types of kidney cells when exposed to aminoglycosides.

Organovo first began bio-printing kidneys in 2015, but their new processes are much faster, allowing 200 mini-kidneys to be produced in 10 minutes. The improvement in speed and quality has opened the doorway for bioprinting entire organs for transplant. “3-D bioprinting can generate larger amounts of kidney tissue but with precise manipulation of biophysical properties, including cell number and conformation, improving the outcome.”

Professor Little said that prior to this study, the possibility of using such technology for transplantation was too complicated to consider. “The pathway to renal replacement therapy using stem cell-derived kidney tissue will need a massive increase in the number of nephron structures present in the tissue to be transplanted,” she said.

“By using extrusion bioprinting, we improved the final nephron count, which will ultimately determine whether we can transplant these tissues into people.”

Source: Medical Xpress

Standing Protects against Heart Failure in Older Women

A study examining elderly women’s amount of time spent sitting or standing has shown a marked increase in the risk for hospitalisation for heart failure.

The Women’s Health Initiative Observational Study followed 81 000 postmenopausal women for 9 years. None of the women had been diagnosed with heart failure and could walk at least one block unassisted, and they self-reported the amount of time they spent sitting or lying down. Over this time, 1402 women were hospitalised with heart failure.

The researchers graded the amount of sedentary time (sitting or lying down) into three categories: 6.5 hours or less; 6.6-9.5 hours; and more than 9.5 hours. Those who sat 9.5 hours or more experienced a 42% increase in the rate of heart failure compared to those who sat for 6.5 hours or less.

Lead author of the study,  Michael J LaMonte, PhD, MPH, research associate professor of epidemiology in the School of Public Health and Health Professions at the University at Buffalo in Buffalo, New York, said that there was a lack of data on sedentary time and heart failure, and even less so in elderly women.

“Our message is simple: sit less and move more. Historically, we have emphasised promoting a physically active lifestyle for heart health—and we should continue to do so! However, our study clearly shows that we also need to increase efforts to reduce daily sedentary time and encourage adults to frequently interrupt their sedentary time.” 

He added, “This does not necessarily require an extended bout of physical activity; it might simply be standing up for 5 minutes or standing and moving one’s feet in place. We do not have sufficient evidence on the best approach to recommend for interrupting sedentary time. However, accumulating data suggest that habitual activities such as steps taken during household and other activities of daily living are an important aspect of cardiovascular disease prevention and healthy aging.”

Source: Medical Xpress

Anaesthetic Clues Hidden in Tarantula Venom

In a finding that promises new research into pain management, a tarantula toxin molecule has been revealed to use a “stinger” to permanently close the voltage sensors on nerve cells’ sodium channels.

Chronic pain is difficult to treat, and attempts to seek relief can sometimes lead to opiate overdose, addiction, prolonged withdrawal, and even death. This means that there is a critical need to develop pain management medications that are safer, more effective and non-addictive. Tarantula toxin is of interest because it has to be fast-acting, shutting down the nerves of the tarantula’s prey and immobilising it before it can escape.

The tarantula toxin’s mechanism of action has proved elusive: the tarantula toxin-ion channel chemical complex has been hard to capture in its functional form. This has made it especially challenging to replicate the calcium-channel blocking effect in a small molecular form suitable for anaesthetic compounds. To overcome this obstacle, the researchers took a toxin-binding region from a specific type of human sodium channel that is key to pain transmission and imported it into their bacterium-derived model ancestral sodium channel. In doing so, they successfully obtained a clear molecular view of the configuration of the potent toxin from tarantula venom as it tightly binds to the sodium channel receptor site.

Prof William Catterall of the University of Washington School of Medicine explains: “Remarkably, the toxin plunges a ‘stinger’ lysine residue into a cluster of negative charges in the voltage sensor to lock it in place and prevent its function. Related toxins from a wide range of spiders and other arthropod species use this molecular mechanism to immobilise and kill their prey.”

The researchers hope that these insights will lead to the development of a new variety of anaesthetic compounds.

Source: News-Medical.Net

SA Medicinal Plants Show a COVID Treatment Promise in New Study

Researchers at the Durban University of Technology and the University of KwaZulu-Natal have been examining plants used in traditional African medicine to see if they have any application in treating COVID.

There has been increasing interest in investigating medicinal plants for compounds to use in the treatment of COVID, which still lacks an effective treatment despite effective vaccines being demonstrated.

The researchers began with 29 compounds from medicinal plants known to be effective in treating the common cold, flu, other respiratory conditions, as well as their antimalarial, antiviral and antioxidant activity.

Using a biocomputational approach that does simulated “molecular docking” with various compounds and the known molecules of SARS-CoV-2, the researchers found a number of plants, including the Rooibos bush, contained useful compounds. These displayed favourable binding orientations and were thus identified as being potential inhibitors of the SARS-CoV-2 receptor binding domain and SARS-CoV-2 RNA-dependent polymerase. Four compounds showed extremely good binding to the virus, indicating that they may prevent viral replication.

The next stage of their work will be an in vitro study, before moving onto animal models but is contingent on the team being able to secure funding.

Source: The Conversation

Inexpensive Oxford COVID Vaccine Proven Effective

A vaccine developed by the University of Oxford has shown to be effective, according to the BBC. The vaccine trial was conducted with over 20 000 volunteers in the UK and Brazil.

The vaccine conferred 70% protection, compared to the 90% and above level from the other two vaccines. However, a small dose followed by a large dose however, conferred 90% protection.   

At £3 (R60) a dose, the Oxford vaccine is less costly than the Pfizer/BioNTech and Moderna vaccines which cost £15 (R300) and £25 (R500) respectively. The Oxford vaccine is also easier from a logistical perspective as it can be stored at higher temperatures. In an encouraging sign for controlling the pandemic, it appears that there were fewer asymptomatic infections with the low-dose-then-high-dose vaccine administration. 

The UK government has four million doses already prepared, and if the vaccine is authorised, the government will roll out an immunisation program on a vast scale. Care home staff, health care workers and the elderly will receive the vaccinations first. Meanwhile, Oxford’s manufacturing partner AstraZeneca is preparing to produce three billion doses. However, logistical challenges remain.

Prof Peter Horby, from the University of Oxford, said, “This is very welcome news, we can clearly see the end of [the] tunnel now. There were no Covid hospitalisations or deaths in people who got the Oxford vaccine.”