Month: December 2021

A Look Back at 2021

Photo by Olya Kobruseva on Pexels

The start of 2021 saw South African hospitals battling for resources amid a COVID surge, and planning for what would be a very controversial and drawn-out vaccination programme which would be partly paid for by the overflowing coffers of the country’s medical aid schemes. Indeed, there was a real concern that the as-yet-to-be-named Beta variant would evade vaccines, which would prove to be true – and a story which would be repeated with the Omicron variant later in the year. In China, the start of an investigation into the origins of the SARS-CoV-2 virus in Wuhan was stymied by the Chinese government denying them entry.

The middle of the year saw the Third Wave, now driven by the highly transmissible Delta variant which had ravaged India earlier in the year. Production setbacks further dogged South Africa’s vaccine programme as millions of Johnson & Johnson vaccines were deemed unfit for use. In Brazil, deaths passed half a million amid condemnation of the mishandling of the COVID pandemic by its President Jair Bolsonaro. Economic frustration, stoked by political manoeuvring around the trial of former President Jacob Zuma, saw much of the country erupt in looting and violence. This would seriously damage COVID vaccination and surveillance efforts in the affected areas, particularly KwaZulu-Natal.

Statins seemed to be losing some of their bad image as new studies revealed that they were not associated with cognitive decline, following on from a 2020 study showing many of their feared side effects were the result of the ‘nocebo’ effect. The US government initiated a probe into how a controversial drug for the treatment of Alzheimer’s disease managed to receive approval despite no evidence of benefit. Dr Zweli Mkhize stepped down as Health Minister amidst revelations about procurement irregularities relating to the Digital Vibes contract.

Towards the end of the year, South African vaccination rates fell due to a combination of factors: vaccine hesitancy, apathy and difficulty servicing remote areas. Omicron was detected in late November, immediately raising alarm due to the extremely large number of mutations it possesses. In response, countries around the world announced immediate travel bans or heightened quarantine restrictions. However, these proved futile as the highly contagious Omicron was already loose in the borders of many countries, rendering the controversial containment efforts moot.

Fortunately, early signs from Netcare showed that Omicron caused less severe disease. By year end, new effective COVID treatments were going through these stages of their final approval. Merck’s Molnupiravir (Lagevrio) had shown promise for the treatment of COVID, though later analysis with additional data showed it to be less effective than believed. Expected production for Pfizer’s nirmatrelvir (Paxlovid) was expected to increase to 80 million courses after results showed an 89% reduction of hospitalisation or death for outpatients. As the year closed, there was some good news for South Africa’s economy as travel bans were lifted – though the countries imposing them now had Omicron surges of their own to contend with.

‘Switching Off’ Over The Holidays is a Good Idea

Photo by Tim Gouw on Pexels

Not properly ‘switching off’ and disconnecting from work-related electronic communications can be more than just annoying, it can damage your health, research shows.

Researchers from the University of South Australia surveyed more than 2200 academics and professional staff across 40 Australian universities, and found that employees who responded to work emails and texts out of hours had greater odds of experiencing burnout, psychological distress, and poor physical health.

Researchers found that in 2021:

  • 26% of employees felt that they had to respond to work-related texts, calls, and emails from supervisors during their leisure time;
  • 57% said that they’d sent work-related digital communications to other colleagues in the evenings;
  • 50% reported that they often receive work-related texts, calls and emails from colleagues on the weekend;
  • 36% reported that it was the norm to respond immediately to digital communication in their organisation.

UniSA researcher Dr Amy Zadow says that the expectations for employees to be available 24-7 is putting pressure on workers.

“Since COVID, the digitalisation of work has really skyrocketed, blurring work boundaries, and paving the path for people to be contactable at all hours,” Dr Zadow said.

“But being available to work both day and night limits the opportunity for people to recover – doing things such as exercise and catching up with friends and family – and when there is no recovery period you can start to burn out.

“Our research shows that high levels of out-of-hours work digital communication can have a significant impact on your physical and mental wellbeing, affecting work-family relationships, causing psychological distress, and poor physical health.

“Conversely, workers who kept their work boundaries in check experienced less stress and pressure.”

The study found that those who were expected to respond to after-hours work communications on the weekends reported higher levels of psychological distress (56% vs 42%); emotional exhaustion (61% vs 42%); and poor physical health (28% compared to 10%).

UniSA’s Professor Kurt Lushington said that dealing with work-related stress is becoming increasingly important.

“Managing out-of-hours communications can be challenging, but organisations do have the power to discourage ‘work creep’,” Prof Lushington said.

“Setting up policies, practices and procedures to protect psychological health by developing a strong Psychosocial Safety Climate is likely to limit damaging out-of-hours digital communication. And, on a broader scale, this is already being considered in various Enterprise Bargaining Agreements and National Employment Standards.

“The starting place is measuring work demand so that an organisation can mitigate the risk in the first place. Once they do this, they can develop protective actions that can prevent the development or continuations of harmful workplace norms.

“At the end of the workday, everyone should have the right to disconnect.”

Source: University of South Australia

Why Omicron May Hit Other Countries Harder

COVID heat map. Photo by Giacomo Carra on Unsplash

South Africa may have gotten off more lightly from Omicron due to widespread immunity from previous infection combined with vaccine coverage, researchers think, which may not bode well for other countries which have not completed their vaccination nor seen the worst COVID surges.

The South African Medical Research Council in collaboration with Discovery Health on Tuesday last week presented data from a large study showing  that South Africans infected with Omicron are, on average, less likely to be hospitalised, and recover faster, compared to the other variants.

Their study looked at more than 200 000 COVID cases in South Africa during a Delta-driven surge in September and October, and the start of the Omicron-driven surge in November, as that variant began increasing rapidly. About a quarter of the people in the study already have a chronic illness, putting them at higher risk of severe COVID.

The researchers found a hopeful trend: The risk of hospitalisation for adults dropped 30% during the early days of the Omicron surge from the levels seen there in September and October.

“The hospital admissions during omicron, standing at 58 per 1000 infections, are the lowest of the four COVID waves, and one-third of what we experienced during the delta surge,” said Discovery Health CEO Ryan Noach.

Why was this so? One explanation could be the immunity from COVID recovery present in the population. South Africa had experienced three huge COVID surges with low vaccination rates compared to the US and Europe.

When the Omicron variant appeared, only about a quarter of the population were vaccinated but the vast majority of residents had likely already been infected with previous variants of SARS-CoV-2. This was based on the excess mortality rate observed in the country through the pandemic, and so it is thought that South Africans likely had some immunity granted by infection.

“Thus, Omicron enters a South African population with considerably more immunity than any prior SARS-CoV-2 variant,” concluded Dr Roby Bhattacharyya, an infectious disease specialist, and epidemiologist William Hanage in a recent working paper. This means that most Omicron cases are likely to be reinfections, rather than first infections.
Other countries will not have as broad a ‘coverage’ of vaccination and previous infection as South Africa. Around 125 million Americans are unvaccinated, and a recent study estimated that about 20% of Americans had been infected with COVID from the start of the pandemic, up to August, 2021.

The data therefore suggest that a minimum of 20% of Americans who are completely ‘naive’, as scientists term it, when it comes to exposure to SARS-CoV-2.

Source: NPR

Most Superheroes Will Age Healthily, Researchers Conclude

Spider-Man has a healthy outlook, so long as he doesn’t binge drink or smoke like his mentor, Iron Man. Source: Pixabay

Australian researchers in the Christmas edition of the British Medical Journal took a whimsical look at the ageing trajectories of Marvel superheroes based on their attributes and behaviours as seen in the films, finding them to be largely well-adjusted and likely to age healthily. 

Positive behaviours and health assets
Marvel superheroes are physically active, socially engaged, and optimistic, with high educational attainment and (with one notable exception) healthy weight, all of which have been associated with a positive ageing trajectory.

The review found that superheroes regularly engage in physical activity and exercise, both associated with healthy ageing. They often undertake high intensity interval training (HIIT), associated with improved health status in ageing men.

Even during discussions about how to stop aliens from enslaving humanity, superheroes stand regularly and pace, increasing their step count and further improving their healthy outlook.

In terms of social engagement, superheroes exhibit a high degree of social cohesion and connectedness, both linked to reduced dementia risk. People with strong social ties tend to live longer than isolated people, regardless of other risk factors such as smoking, alcohol consumption, and physical activity.

The superheroes show a positive or optimistic mindset on several occasions, as well as psychological resilience and a sense of purpose, all of which have been associated with healthy ageing.  Some have traumatic backgrounds, including Spider-Man who was orphaned, which increases his risk of substance abuse and mental health problems. However, his supportive social contacts, including positive male role models help mitigate this.

Most of the superheroes did not drink or smoke excessively, save for Iron Man and Thor, which is associated with longevity and healthy ageing. However, Thor is already thousands of years old and the researchers could not assume that modifiable personal traits would affect his life trajectory.

Negative behaviours and risk factors
Superheroes are exposed to loud noises, air pollution, and receive multiple head injuries precipitated by high risk physical activities.

Superheroes are repeatedly exposed to loud noises such as explosions, which is linked to hearing loss, which in turn is associated with an increased risk of cognitive impairment and dementia. Some of the superheroes, such as Hulk and Thor, have booming voices, potentially indicative of early sensorineural hearing loss.

During their activities, superheroes sustain multiple major head injuries, increasing their dementia risk. Involvement in high risk activities, which could increase their likelihood for life changing physical injury and disability.

Of the individual cases presented, Black Panther has probably the best health outlook, as he is extremely wealthy and intelligent, health assets that he shares in common with Iron Man. However, unlike Iron Man, he does not drink or smoke excessively, and is a vegetarian, which has well-studied benefits in healthy ageing.

On the other end of the spectrum, the Hulk was noted to have serious health concerns. Bruce Banner transforms to the Hulk when he experiences tachycardia—specifically, a heart rate of 200 beats per minute. The frequency of this occurrence suggests a predisposition to cardiac arrhythmias, possibly indicating underlying cardiac disease.

Hulk’s body mass index (BMI) is about 120 (calculated from height 213cm–243cm and weight 471kg–635kg). Although being in the overweight category might be protective, obesity is associated with a higher death rate as well as dementia, and several chronic health conditions and frailty. Hulk’s BMI also raises pragmatic concerns around future access to appropriate healthcare. Hulk’s almost constant anger (“That’s my secret Captain. I’m always angry”) might lead to increased inflammation and comorbidity in advanced old age.

Source: The British Medical Journal

Why Cancer Cells Linger to Create Metastatic Cancer

Colon cancer cells. Source: National Cancer Institute on Unsplash

A major mystery in cancer research has been solved: How cancer cells remain dormant for years after leaving a tumour before awakening to create metastatic cancer.

According to findings by Mount Sinai researchers which were reported in Nature Cancer, the cells remain quiet by secreting a type of collagen, called type III collagen, in the environment around themselves, and only turn malignant once the level of collagen tapers off. The researchers found that by enriching the environment around the cells with this collagen, they could force the cells to remain in a dormant state and prevent tumour recurrence.

“Our findings have potential clinical implications and may lead to a novel biomarker to predict tumour recurrences, as well as a therapeutic intervention to reduce local and distant relapses,” said senior author Jose Javier Bravo-Cordero, PhD, Associate Professor of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. “This intervention aimed at preventing the awakening of dormant cells has been suggested as a therapeutic strategy to prevent metastatic outgrowth. As the biology of tumour dormancy gets uncovered and new specific drugs are developed, a combination of dormancy-inducing treatments with therapies that specifically target dormant cells will ultimately prevent local recurrence and metastasis and pave the way to cancer remission.”

Most cancer deaths result from metastases, which can occur several years after removal of a tumour. Previous work looked at how dispersed tumour cells awaken from dormancy; this new work showed how the cells remain dormant.

The study used high-resolution imaging techniques, including intravital two-photon microscopy, a technology that allows the visualisation of dormant cells in their environment in real time in a living animal. This technology allowed the researchers to track dormant tumour cells in mouse models using cancer cell lines. By using this technology, the researchers were able to visualise the changes in the architecture of the extracellular matrix as tumour cells became dormant and how it changed when these cells awoke.

The researchers demonstrated that an abundance of the collagen could potentially be used as a predictor of tumour recurrence and metastasis. In the mouse models, when type III collagen was increased around cancer cells that had left a tumour, cancer progression was interrupted and the disseminated cells were forced into a dormant state. Similar to wound treatment, in which collagen scaffolds have been proposed to treat complex skin wounds, this study suggests that by enriching the tumour microenvironment in type III collagen, metastasis may be prevented by sending tumour cells into a dormant state.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Convalescent Plasma was Effective in Early Pandemic

Convalescent plasma from COVID patients was likely of benefit to patients early on in the pandemic, before the introduction of remdesivir and corticosteroids as treatments, according to results of a landmark study published in JAMA Internal Medicine.

The randomised clinical trial, CONTAIN COVID-19, was established to evaluate the safety and efficacy of convalescent plasma in hospitalised coronavirus patients. Overall, the trial showed that convalescent plasma was safe and well tolerated. It worked best in the early days of the pandemic, when plasma had higher antibody levels, when it was given early in the disease, and particularly for immunosuppressed people.

“This landmark study shows once and for all that convalescent plasma is an important countermeasure early in a pandemic when no other therapies are available. It was an important finding that lays the foundation for the rapid response to future pandemics,” said Luis Ostrosky, MD, professor and director of the Division of Infectious Diseases at McGovern Medical School at UTHealth Houston. “This trial, the largest of its kind, also showed that with proper funding and structure, researchers across the country were able to come together quickly in the middle of a global crisis to explore this therapeutic intervention.”

Trial results also showed a drop in efficacy after the introduction of remdesivir and corticosteroids, and by the end of the 11-month trial, there was no difference in outcome between plasma and placebo in patients at 14 and 28 days. However, patients on corticosteroids, but not remdesivir, appeared to benefit from convalescent plasma at day 14.

Since the patient characteristics, available treatments, and the virus, all changed over time, subgroup analyses were done, which showed a possible benefit for patients in the first quarter of the trial, a period from April to June 2020.

Participants in that first quarter were older, less severely ill, had a longer duration of symptoms, and received high-titer plasma. Shorter symptom duration can indicate a more severe case of the viral infection.

“Convalescent plasma could be an important early treatment tool in places that don’t have access to monoclonal antibodies, corticosteroids, remdesivir, or other therapies,” said the study’s co-investigator, Professor Bela Patel, MD. “It should also be considered for patients who are immunosuppressed and those whose B cell function is compromised.”

The researchers also suggested that, in addition to the introduction of corticosteroids and remdesivir, the decrease in efficacy over time may have been due to using convalescent plasma that originated from New York City before the emergence of other SARS-Co-V-2 variants .

Source: University of Texas Health Science Center at Houston

Why COVID Cases Vary in Severity

Source: Fusion Medical Animation on Unsplash

Researchers working with ‘humanised mice’ have found why some mild cases of COVID tip over into more severe and life-threatening disease.

An estimated 80 to 90% of people infected with COVID experience only mild cases while 10 to 20% face more severe or life-threatening symptoms.

Yale University researchers working with mice they have engineered to possess human-like immune systems may have found why this is so. Their findings,  published in Nature Biotechnology revealed that the causes of severe COVID may lie in our own antiviral inflammatory response to the virus.

The study also showed that two well-known therapies, monoclonal antibodies and the steroid dexamethasone, can help treat COVID infections. But in the case of the antibodies, treatment is only effective if administered early in the course of disease. In the case of steroids, it’s only effective if administered during later stages of the disease.

Standard laboratory animals and humans have different immune responses, which has made it difficult for scientists to pinpoint the tipping point between mild and severe cases of COVID, so mice engineered to have a human-like immune system, were able to offer an answer.

“If you infect a standard laboratory mouse with SARS-CoV-2 they will get infected, but not get seriously ill,” said Flavell, Sterling Professor of Immunobiology at Yale and senior author of the paper. “But our humanised mice get sick and just don’t get better. Their whole immune system is on fire.”

The research team introduced SARS-CoV-2 virus taken from seriously ill human patients into the nasal passages of their humanised mice and then followed the course of the disease.

They found that the infected mice exhibited the same symptoms as severely ill human patients, such as lung damage, weight loss, and a heightened, persistent inflammatory immune response that damages tissues. They then treated the mice with monoclonal antibodies which specifically target the virus, and were  found to be effective if given before or very early after infection but did little to stifle symptoms if administered in later stages of infections.

Conversely, during the early stages of infection the immune suppressant dexamethasone was fatal to mice when it suppressed the initial immune response that was crucial to combat the virus. However, during later stages of disease, it helped clear infection  by suppressing the inflammatory response that had begun damaging organs.

“Early in the course of disease, a strong immune response is crucial for survival,” said first author Esen Sefik. “Later in the disease, it can be fatal.”

The humanised mice models might also reveal strong clues to the causes and potential treatments of so-called long and severe COVID, the scientists said.

Source: Yale University

Trial Shows Dupilumab is Safe and Effective for Asthma in Children

Source: PIxabay/CC0

In a late-stage clinical trial, the biologic agent dupilumab reduced the rate of severe asthma attacks and improved lung function and asthma control for children ages 6 to 11, adding to the treatment options for children with moderate-to-severe asthma. 

The findings of the international multicentre Liberty Asthma VOYAGE trial, appeared in the New England Journal of Medicine, and informed the agent’s approval in this age group by the Food and Drug Administration.

“This is a really important advance for children with moderate-to-severe asthma and their families,” said Leonard Bacharier, MD, an asthma specialist at Monroe Carell Jr. Children’s Hospital at Vanderbilt and the international lead investigator for the trial.

Asthma is the most common chronic disorder of childhood, according to the Centers for Disease Control and Prevention. It is a leading cause of hospitalisation for children, and children with moderate-to-severe asthma may have reduced lung function and be at greater risk for lung diseases in adulthood, said Dr Bacharier.

“As asthma gets increasingly severe, the burden becomes substantial, impacting the child and the entire family,” he said. “While we have very good asthma therapies available, none of them are perfect in eliminating severe exacerbations.”

Dupilumab, a monoclonal antibody that targets type 2 inflammation, has been approved for the treatment of asthma in adults and adolescents for several years. Based on its established safety and efficacy, the investigators conducted a Phase III clinical trial in 408 children aged 6 to 11 who had uncontrolled moderate-to-severe asthma.

In a double-blind trial, children received either a subcutaneous injection of dupilumab or placebo in addition to their standard therapy every two weeks for a year.

Most participants had markers of type 2 inflammation, namely elevated levels of immune cells called eosinophils and/or elevated levels of nitric oxide in exhaled air. In patients with these markers, dupilumab significantly reduced the rate of severe exacerbations – symptoms requiring systemic steroid treatment, need for emergency care or hospitalisation – by nearly 60%. Additionally, dupilumab improved lung function, measured by forced exhalation, and improved asthma control.

“This is the first study of its kind in children ages 6 to 11 that has demonstrated that a biologic improves asthma exacerbations, lung function and asthma control,” Dr Bacharier said. “We were not surprised, because dupilumab was very effective in clinical trials in adults and adolescents, but we were delighted with the results and the hope they bring to children and their families.”

The trial demonstrated that dupilumab was safe. Some children in the treatment  arm had increases in blood eosinophil levels or mild but manageable parasitic infections (type 2 immunity fights parasites), but very few discontinued dupilumab because of adverse reactions.

Limited ethnic diversity was noted as a weakness in the trial, especially in light of the disproportionate asthma burden among Black people. Trial participants were invited to participate in a trial extension to determine long-term safety and efficacy.

While two other biologic medicines targeting type 2 inflammation have been approved for asthma treatment in children, neither has shown improvements in all three key clinical endpoints – asthma exacerbations, lung function and asthma control – in a controlled clinical trial, Dr Bacharier said.

Bacharier plans to explore the potential for dupilumab to modify asthma development. “Can we use this agent earlier in life to change how the disease develops? I think that’s the next frontier,” he said.

Source: EurekAlert!

Scientists Find Epilepsy Biomarker in Autistic Children

Photo by Ben Wicks on Unsplash

Scientists have discovered that an important brain protein that quiets overactive brain cells and is abnormally low in children with autism, which may explain why so many children with autism also have epilepsy. The findings were published in Neuron.

This protein can be detected in the cerebrospinal fluid, making it a promising marker to diagnose autism and potentially treat the epilepsy that accompanies the disorder.

Mutated versions of this gene were known to cause autism combined with epilepsy, and epilepsy appears in 30% to 50% of children with autism. Autism, which is 90% genetic, affects 1/58 children in the US.

Appropriately nicknamed ‘catnap2’, the protein, CNTNAP2, is produced by the brain cells when they become overactive. Because the brains of children with autism and epilepsy lack sufficient CNTNAP2, scientists found, their brains become overactive, leading to seizures.

For the study, the researchers analysed the cerebrospinal fluid in individuals with autism and epilepsy, and in mouse models. Though, cerebrospinal fluid has been used in researching disorders such as Parkinson’s, this is the first study showing it is an important biomarker in autism.

The new finding about CNTNAP2’s role in calming the brain in autism and epilepsy may lead to new treatments.

“We can replace CNTNAP2,” said lead study author Peter Penzes, the director of the Center for Autism and Neurodevelopment at Northwestern University Feinberg School of Medicine. “We can make it in a test tube and should be able to inject it into children’s spinal fluid, which will go back into their brain.”

Penzes’ lab is currently working on this technique in preclinical research.

The level in the spinal cord is proxy for the level in the brain, explained Penzes. When brain cells are too active because of overstimulation, they produce more CNTNAP2, which floats away and binds to other brain cells to calm them. The protein also leaks into the cerebrospinal fluid, where scientists were able to measure it, giving them a clue for how much is produced in the brain.

Source: EurekAlert!

Metformin Ineffective in Most Breast Cancers

Breast cancer cells. Image source: National Cancer Institute on Unsplash

Researchers have found that the diabetes drug metformin, once hoped to hold enormous promise in treating breast cancer, does not prevent or stop the spread of the most common forms of the disease but may still have potential in HER2-positive breast cancer.

The randomised, double-blind trial enrolled 3600 patients who received two pills a day of either placebo or metformin. Overall, researchers found the addition of metformin to standard breast cancer treatments did not improve outcomes in the two most common types of breast cancer, hormone receptor-positive or negative.

“The results tell us that metformin is not effective against the most common types of breast cancer and any off-label use of this drug for the treatment of these common types of breast cancer should be stopped,” said Pamela Goodwin, a professor in the department of medicine at the University of Toronto’s Temerty Faculty of Medicine.

Prof Goodwin presented the findings at the 2021 San Antonio Breast Cancer Symposium.

While metformin was found not to be effective in treating the most common forms of breast cancer, there was evidence that use of metformin for five years might lead to a reduction in deaths from HER2-positive breast cancer, a less aggressive subtype which makes up about 20% of all breast cancers.

“Metformin is not beneficial for use in most common breast cancers, but in the cases of HER2 positive breast cancer, our findings suggest it may be beneficial,” said Prof Goodwin. “These results need to be replicated in future research before metformin is used as a breast cancer treatment, however, it could provide an additional treatment option for HER2-positive breast cancer,” she added

Previous studies suggested metformin may also reduce the risk of development and increase survival of some cancers, including breast cancer.

Metformin was theorised to slow breast cancer growth by improving patient metabolism, notably insulin levels, leading to reduced cancer cell growth, or that it might impact cancer cells directly.

Next steps would be to prospectively test the impact of metformin in patients with HER2-positive breast cancer in a randomised clinical trial. 

Source: University of Toronto