By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262
According to results from the SELECT trial run by Novo Nordisk, semaglutide dramatically reduces the risk of major adverse cardiovascular events (MACEs) in addition to its obesity benefits. This is bolstered by the results of another trial, STEP-1, which also suggested significant reduction in future cardiovascular events. These results have captured the attention of researchers, who commented in Nature that they could change the practice of cardiology.
Semaglutide, sold in the US for the treatment of both obesity (Wegovy) and diabetes (Ozempic), is an agonist for glucagon-like peptide 1 (GLP-1), a hormone associated with appetite.
”It’s hard to think of other [drugs], apart from statins, that have shown such a profound effect,” says Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, USA.
It was expected that semaglutide would have cardiovascular benefits through promoting weight loss, but evidence shows that drugs mimicking GLP-1 can improve fatty-acid metabolism and reduce inflammation, for example, says Gulati. “This is what’s so fascinating about these drugs. They work on the brain, the pancreas, the cardiovascular system, the gastrointestinal tract … There’s more to them than simply weight loss.”
Recent studies have been encouraging in terms of semaglutide’s benefits for reducing cardiovascular disease risk. Earlier this month, Novo Nordisk announced the headline results from the SELECT cardiovascular outcomes trial. The double-blinded trial compared subcutaneous once-weekly semaglutide 2.4mg with placebo as an adjunct to standard of care for prevention of MACEs over a period of up to five years. The trial enrolled 17 604 adults aged 45 years or older with overweight or obesity and established cardiovascular disease (CVD) with no prior history of diabetes.
The trial showed 20% reduction in MACEs for people treated with semaglutide 2.4mg compared to placebo. The primary endpoint was a composite outcome of the first occurrence of MACE cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. All three of these components contributed to the MACE reduction. 1270 first MACEs were accrued.
Expanding GLP-1 analogues to cardiovascular disease prevention may not be without challenges, as the European Medicines Agency opened investigations into semaglutide and liraglutide over reports of suicidal thoughts and self-harm.
A separate study based on the STEP 1 trial data found that 93 million adults in the US could benefit from semaglutide, from a combination of weight loss and reduced cardiovascular benefits. They estimate a reduction in relative risk of 18% with the drug.
Dr Mark Blaylock, medical manager at Manguzi Hospital. PHOTO: Supplied.
By Sue Segar for Spotlight
There was a time, about 20 years ago, when, at the Manguzi district hospital in Northern KwaZulu-Natal, (and, of course, at hospitals throughout South Africa too) mothers and their babies were dying of AIDS at shockingly high rates.
“We used to get these patients who were slow progressors,” Mark Blaylock, medical manager at Manguzi, tells Spotlight. “Then there were the rapid progressors – babies who were HIV-positive who would get sick very quickly. There wasn’t much we could do for them. We’d give them vitamins and Bactrim, but ultimately they died. Then we had the ones who got sick a bit later, and those were even worse because now mum has had this baby for five years and they’ve bonded, and are a little family and now they are coming in with AIDS. Obviously, a huge number of mums died too. It was heartbreaking.
“It was the pregnancies that knocked their vulnerable immune systems. We’d watch it over and over again. The mums would come in looking ok and then they’d get pregnant and just go downhill. This was in the pre-ARV era. Pregnancy was a death sentence. I think people have forgotten what it was like in those days.”
Blaylock is talking to Spotlight from Northern KwaZulu-Natal, relaying how things have changed for the better since that terrible era. “It’s quite astounding,” he says. Blaylock returned to the hospital ten years ago after having been away for four.
“I was going through the stats recently, and in those days, 40 percent of all mothers who delivered were HIV positive, and about 40 percent of those babies born to HIV- positive mothers ended up with HIV either from birth or breastfeeding. About 20 percent would pick up HIV at birth and another 20 percent would pick it up subsequently through breastfeeding.
“These days, if we have one baby who is delivered HIV-positive or who picks up HIV, we get really upset. Our six-month HIV-positive rate now for babies is less than 0.6 percent and that is a dramatic change. It makes me so happy. Unfortunately, the young girls are still positive, but at least their babies are not becoming positive.”
Blaylock puts the changes down, “purely”, to prevention of mother-to-child transmission (PMCT) using antiretroviral therapy (ART). “Remember how, at one stage, we only gave HIV treatment if a patient was below a certain CD4 count? That was changed to test-and-treat, so regardless of their CD4 count, patients will get HIV treatment which brings the viral load down dramatically,” he says. “And now we have dolutegravir (an ARV), which is the backbone of our current HIV treatment. The success is due to prevention of mother-to-child transmission (PMTC) as well as the test-and-treat policy.”
‘A mixed bag’
It’s Sunday, a day off for Blaylock, and he’s speaking from a place with the best reception near his house on the edge of the Shengeza Lake. He lives here with his wife, Liz and their 13-year-old home-schooled daughter, Una. The sound of birds in the background makes it hard to hear him on the call. “It’s peaceful. There are hippos all around and lots of birds. It’s Eskom-free, which is even better. I love it. We live with three dogs, three cats, a genet, and I can’t tell you how many snakes. It’s paradise.”
It’s taken a long time to clinch this interview, but Blaylock has finally relented and forwarded us the provincial health department’s media protocol he has to adhere to. On problems in KwaZulu-Natal’s health system, he is reticent, saying only that it’s a “mixed bag”. “There’s a lot of dead wood, but there are real areas of excellence,” he says.
His reticence is understandable.
There was a time, also about 15 years ago, amidst the noise and turmoil of the last few years of state-backed AIDS denialism, when Blaylock was going through his own personal trauma. In April 2008, whilst working as chief medical officer at Manguzi, he was suspended for throwing an official photograph of then-Health MEC Peggy Nkonyeni into a dustbin in the hospital’s foyer. He did this out of anger and frustration, after his colleague at the hospital, Colin Pfaff was charged with misconduct for sourcing funding for antiretroviral drugs for pregnant women, and for implementing dual antiretroviral therapy to save babies from HIV – because politicians were not doing so.
He was also furious about comments made by Nkonyeni, questioning the integrity of rural doctors and suggesting they were racist. The South African National AIDS Council soon after asked the Human Rights Commission to probe the ‘racial tone’ of Nkonyeni’s remarks and to curb her ‘harassment’ of Manguzi doctors.
At the time, Blaylock (and Pfaff) were hailed by many working in the health sector as heroes with a deep commitment to their patients. In a letter to the provincial health department at the time, Blaylock said he had given his “heart and soul” to the under-resourced hospital, going beyond the call of duty.
Needing a change
Blaylock was reinstated but, in December 2008, he decided to leave, saying he needed a change and because the KwaZulu-Natal Department of Health was in “absolute disarray”. He says his old colleague Pfaff went to work as a missionary doctor in Malawi.
There was more to Blaylock’s decision to leave Manguzi than just the public disagreement with Nkonyeni. In our interview, he describes those days as “a really tough decade”. “Working in paediatrics, as I did for my first couple of years at Manguzi, I couldn’t take it anymore, emotionally. I just couldn’t do it, so I taught myself surgery. That was easier, as you could fix people. We were also so broken from losing so many friends, colleagues, and patients from HIV at the time. It was definitely traumatising and emotionally exhausting, not just for me but for Liz.
“There’s no doubt most of us were burnt out,” he says. “We kind of knew it, but we pushed on anyway. We were also quite a bit wilder and younger. We’d blow off steam by recklessly taking tiny boats across the lake, in the big waves, with lots of hippos – or we’d go for runs along the beach or naked midnight swims.”
The years outside SA
After leaving Manguzi, Blaylock moved to Ghana, where he took up a position as a general doctor at ABA Hospital in Tarkwa, north-east of Accra. “The hospital was part of the national health system but contracted to a mine, so we would treat people and then try and charge the government, fairly unsuccessfully, for the treatment,” he says. “I’d always fancied the idea of Ghana. I had this fantasy about Kwame Nkrumah and it being the first country to throw off Britain in Africa – but I didn’t enjoy it as much as I’d hoped. Everywhere you went, the police were pulling you over and asking for bribes.”
A defining moment was when Blaylock says he noticed the anti-malaria medication the hospital was giving patients was “just not working”. “Our malaria patients kept coming back full of parasites. I knew there were similar drugs in South Africa which were fantastic, so there was definitely something wrong.” He says he sent a sample to South Africa for testing and realised that “they weren’t as full of the good stuff as they were meant to be”. “I handed in the report and said ‘deal with it.”
From Ghana, where he married Liz and where his daughter Una was born, the family moved to the Kansanshi Mine Hospital in Zambia where they lived on a “beautiful golf estate, surrounded by poverty”.
“It didn’t feel right at all and was quite unfulfilling work,” he recalls. “I did GP work and there was lots of babbalaria – that’s when mostly the expat wives have a hangover on a Monday morning and they think they have malaria.”
Being “medically bored” in Zambia, Blaylock returned to Newcastle in KZN with the aim of specialising in anaesthetics. He worked in Madadeni Hospital’s anaesthetics department, before getting into a registrar’s programme on the anaesthetics circuit at various hospitals in Durban.
‘Like walking back home’
Then, in 2012, his friend and colleague Etienne Immelman, then working as medical manager of Manguzi, suggested that Blaylock should “come home”. “Etienne had been at Manguzi for more than 20 years when he retired six years ago. We’d always had a friendship and a mutual loyalty. He wanted someone to take over.”
Blaylock decided that indeed, it was time. It meant losing the opportunity to specialise, but he says it “felt right”. He went back as medical officer, before becoming manager.
“When I first arrived back, we were a small team, working hard. We all had the same commitment. It gave me a sense of purpose and belonging which hasn’t left.”
Blaylock said the hospital went through a “wonderful period” with a core team of great doctors. “But I burnt them all out during COVID – we had 164 deaths, but we pulled a lot of people through and many of the doctors have moved on. We have a young team now and they are getting there, but we don’t have the broad skill range we used to have. That is common across most district hospitals nowadays.”
So, is he happy to have come full circle, back to the place that was once a source of deep distress to him? “Yes,” he says. “For me, it’s about the community. This place gives me that, as well as a sense of stability and purpose. If you go into a little shop in Manguzi, everyone knows who you are. You say hallo to each other. You shout at a taxi driver and he says, ‘Hey Mark, don’t be so naughty’. When I came back ten years ago, it was like walking back home. It’s just a nice feeling.”
He says a lot has changed in the area. “People say there’s been no development, but when I first arrived at Manguzi in 2002, we knew every car on the road. Today, the town is overwhelmed with vehicles. There’s more money around. We almost never see malnutrition anymore. A lot of government programmes are working, as much as we like to diss them.”
Taking a stand
Given the toll that taking a stand has taken on doctors like Blaylock and Pfaff, one might be forgiven for wondering whether it was all worth it.
Did it make a difference to how things turned out? “Absolutely,” says Blaylock. “There were people scattered people around South Africa at the time who were doing great things. In our part of the world, it was Victor Friedland at Mseleni Hospital and Colin Pfaff (at Manguzi) who were the big drivers, pushing for the right actions to provide the services that the HIV Clinicians Society at the time thought was the correct one and was affordable. The Western Cape had already started, so we weren’t doing anything that groundbreaking except that it hadn’t been official policy yet,” he says.
“Can you believe that when HIV treatment first came to South Africa, it was going to be done at tertiary hospitals only? Imagine the repercussions for us sending a patient to Durban – in those days the Hluhluwe road was 160 kilometres of dirt road – to go and get their HIV treatment once a month. It was not sustainable.
“The HIV (Clinicians) Society pushed hard to get it decentralised to all hospitals. Then it was just going to be done by doctors and they said we absolutely cannot do it just with doctors. It has to be a nurse-run programme. Their vision became our current system. They weren’t the only people, but they were at the forefront of it at the time.”
‘Keeping it going’
Apart from the many advances in HIV treatment, much else has changed at Manguzi over the last 15 years. Blaylock says these days the hospital’s gastro wards are empty “thanks to the rotavirus vaccine”. “We’ve also seen a turnaround in acute respiratory tract infection,” he says. “The pneumococcal conjugate vaccine has changed that dramatically. We have also seen the pushing out of Continuous Positive Pressure Airway Ventilation (CPAP) for neonatal respiratory distressed newborns to district hospitals. This is a non-invasive way of ventilating babies with immature lungs,” he says.
“Our next great hope is the HPV vaccine, which will be a groundbreaker. It’s been rolled out in the past couple of years, but we’ll only see the effects in ten years or so because cervical cancer takes a few decades to come about. The other thing I really want to get in,” he insists, “is that our therapy department (offers occupational therapy, speech and hearing, and physiotherapy) at Manguzi is astonishingly fantastic. There are a lot of good things happening,” he says. “It is so easy to sit on the things that irritate you, but it is worth trying to remember the wins.”
As with several other rural doctors Spotlight has interviewed over the years, Blaylock seems deeply committed to building on what works at Manguzi and simply getting things done. As he says, “When you’ve invested so much into a hospital, you want to keep going as much as you can.”
A new study suggests that depression after traumatic brain injury (TBI) could be a clinically distinct disorder rather than traditional major depressive disorder. The findings, which are published in Science Translational Medicine, hold important implications for patient treatment.
“Our findings help explain how the physical trauma to specific brain circuits can lead to development of depression. If we’re right, it means that we should be treating depression after TBI like a distinct disease,” said corresponding author Shan Siddiqi, MD, from Brigham and Women’s Hospital,. “Many clinicians have suspected that this is a clinically distinct disorder with a unique pattern of symptoms and unique treatment response, including poor response to conventional antidepressants – but until now, we didn’t have clear physiological evidence to prove this.”
Siddiqi, who led the study, was motivated by a patient he shared with David Brody, MD, PhD, a co-author on the study and a neurologist at Uniformed Services University. The two started a small clinical trial that used personalised brain mapping to target brain stimulation as a treatment for TBI patients with depression. In the process, they noticed a specific pattern of abnormalities in these patients’ brain maps.
The current study included 273 adults with TBI, usually from sports injuries, military injuries, or car accidents. People in this group were compared to other groups who did not have a TBI or depression, people with depression without TBI, and people with posttraumatic stress disorder. Study participants went through a resting-state functional connectivity MRI, a brain scan that looks at how oxygen is moving in the brain. These scans gave information about oxygenation in up to 200 000 points in the brain at about 1000 different points in time, leading to about 200 million data points in each person. Based on this information, a machine learning algorithm was used to generate an individualised map of each person’s brain.
The location of the brain circuit involved in depression was the same among people with TBI as people without TBI, but the nature of the abnormalities was different. Connectivity in this circuit was decreased in depression without TBI and was increased in TBI-associated depression. This implies that TBI-associated depression may be a different disease process, leading the study authors to propose a new name: “TBI affective syndrome.”
“I’ve always suspected it isn’t the same as regular major depressive disorder or other mental health conditions that are not related to traumatic brain injury,” said Brody. “There’s still a lot we don’t understand, but we’re starting to make progress.”
With so much data, the researchers were not able to do detailed assessments of each patient beyond brain mapping. To overcome this limitation, investigators would like to assess participants’ behaviour in a more sophisticated way and potentially define different kinds of TBI-associated neuropsychiatric syndromes.
Siddiqi and Brody are also using this approach to develop personalized treatments. Originally, they set out to design a new treatment in which they used this brain mapping technology to target a specific brain region for people with TBI and depression, using transcranial magnetic stimulation (TMS). They enrolled 15 people in the pilot and saw success with the treatment. Since then, they have received funding to replicate the study in a multicentre military trial.
“We hope our discovery guides a precision medicine approach to managing depression and mild TBI, and perhaps even intervene in neuro-vulnerable trauma survivors before the onset of chronic symptoms,” said Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine, and co-author on the study.
A study of nearly 9000 older people in Japan found that those who have little social contact with others may be more likely to have reduction of overall brain volume, and in areas of the brain affected by dementia, compared with those who have more frequent social contact. The study results were published in Neurology.
“Social isolation is a growing problem for older adults,” said study author Toshiharu Ninomiya, MD, PhD, of Kyushu University in Fukuoka, Japan. “These results suggest that providing support for people to help them start and maintain their connections to others may be beneficial for preventing brain atrophy and the development of dementia.”
The study involved 8896 people without dementia, average age 73. They had MRI brain scans and health exams, and were asked how often they were in contact with friends or relatives that did not live with them.
The people with the lowest amount of social contact had overall brain volume that was significantly lower than those with the most social contact. The total brain volume, or the sum of white and grey matter, as a percentage of the total intracranial volume, or the volume within the cranium, including the brain, meninges, and cerebrospinal fluid, was 67.3% in the lowest contact group compared to 67.8% in the highest contact group. They also had lower volumes in areas of the brain such as the hippocampus and amygdala that play a role in memory and are affected by dementia.
The researchers took into account other factors that could affect brain volume, such as age, diabetes, smoking and exercise.
The socially isolated people also had more small areas of damage in the brain, called white matter lesions, than the people with frequent social contact. The percentage of intracranial volume made up of white matter lesions was 0.30 for the socially isolated group, compared to 0.26 for the most socially connected group.
The researchers found that symptoms of depression partly explained the relationship between social isolation and brain volumes. However, symptoms of depression accounted for only 15% to 29% of the association.
“While this study is a snapshot in time and does not determine that social isolation causes brain atrophy, some studies have shown that exposing older people to socially stimulating groups stopped or even reversed declines in brain volume and improved thinking and memory skills, so it’s possible that interventions to improve people’s social isolation could prevent brain volume loss and the dementia that often follows,” Ninomiya said.
Since the study involved only older Japanese people, a limitation is that the findings may not be generalisable to people of other ethnicities and younger people.
People who have low bone density may have an increased risk of developing dementia compared to people who have higher bone density, according to a study of over 3500 people published in Neurology. As an observational study, it only shows an association and cannot prove that low bone density causes dementia.
“Low bone density and dementia are two conditions that commonly affect older people simultaneously, especially as bone loss often increases due to physical inactivity and poor nutrition during dementia,” said study author Mohammad Arfan Ikram, MD, PhD, of the Erasmus University Medical Center in Rotterdam, Netherlands. “However, little is known about bone loss that occurs in the period leading up to dementia. Our study found that bone loss indeed already occurs before dementia and thus is linked to a higher risk of dementia.”
The study involved 3651 people in the Netherlands with an average age of 72 who did not have dementia at the start of the study. Over an average of 11 years of follow-up, 688 people or 19% developed dementia.
X-rays were used to identify bone density, and participants were interviewed every four to five years and completed physical tests such as bone scans and tests for dementia.
Of the 1211 people with the lowest total body bone density, 90 people developed dementia within 10 years, compared to 57 of the 1211 people with the highest bone density.
After adjusting for factors such as age, sex, education, other illnesses and medication use, and a family history of dementia, researchers found that within 10 years, people with the lowest total body bone density were 42% more likely to develop dementia than people in the highest group.
“Previous research has found factors like diet and exercise may impact bones differently as well as the risk of dementia,” Ikram added. “Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss. It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care.”
A limitation of the study is that participants were primarily of European origin and age 70 or older at the start of the study, so these findings may vary in different races, ethnicities, and younger age groups.
Specific receptors in the ears of mosquitoes have been revealed to modulate their hearing, finds a new study led by researchers at UCL and University of Oldenburg. Since male mosquitoes need to hear female mosquitoes is a crucial factor in their reproduction, this discovery could help develop new insecticides and control the spread of harmful diseases, such as malaria, dengue, and yellow fever.
In the study, published in Nature Communications, the researchers focused on a signalling pathway involving a molecule called octopamine. They demonstrated that it is key for mosquito hearing and mating partner detection, and so is a potential new target for mosquito control.
Male mosquitoes acoustically detect the buzz generated by females within large swarms that form transiently at dusk.
As swarms are potentially noisy, mosquitoes have developed highly sophisticated ears to detect the faint flight tone of females amid hundreds of mosquitoes flying together.
However, the molecular mechanisms by which mosquito males ‘sharpen their ears’ to respond to female flight tones during swarm time have been largely unknown.
The researchers looked at the expression of genes in the mosquito ear and found that an octopamine receptor specifically peaks in the male mosquito ear when mosquitoes swarm.
The study found that octopamine affects mosquito hearing on multiple levels. It modulates the frequency tuning and stiffness of the sound receiver in the male ear, and also controls other mechanical changes to boost the detection of the female.
The researchers demonstrated that the octopaminergic system in the mosquito ear can be targeted by insecticides. Mosquito mating is a bottleneck for mosquito survival, so identifying new targets to disrupt it is key to controlling disease-transmitting mosquito populations.
Clinicians are all too familiar with the ‘Google patient’ who finds every scary, worst-case or outright false diagnosis online on whatever is ailing them. During COVID, misinformation spread like wildfire, eroding the public’s trust in vaccines and the healthcare profession. But now, AI models like ChatGPT can be whispering misleading information to the clinical researchers trying to produce real research.
Researchers from CHU Sainte-Justine and the Montreal Children’s Hospital recently posed 20 medical questions to ChatGPT. The chatbot provided answers of limited quality, including factual errors and fabricated references, show the results of the study published in Mayo Clinic Proceedings: Digital Health.
“These results are alarming, given that trust is a pillar of scientific communication. ChatGPT users should pay particular attention to the references provided before integrating them into medical manuscripts,” says Dr Jocelyn Gravel, lead author of the study and emergency physician at CHU Sainte-Justine.
Questionable quality, fabricated references
The researchers drew their questions from existing studies and asked ChatGPT to support its answers with references. They then asked the authors of the articles from which the questions were taken to rate the software’s answers on a scale from 0 to 100%.
Out of 20 authors, 17 agreed to review the answers of ChatGPT. They judged them to be of questionable quality (median score of 60%). They also found major (five) and minor (seven) factual errors. For example, the software suggested administering an anti-inflammatory drug by injection, when it should be swallowed. ChatGPT also overestimated the global burden of mortality associated with Shigella infections by a factor of ten.
Of the references provided, 69% were fabricated, yet looked real. Most of the false citations (95%) used the names of authors who had already published articles on a related subject, or came from recognised organisations such as the Food and Drug Administration. The references all bore a title related to the subject of the question and used the names of known journals or websites. Even some of the real references contained errors (eight out of 18).
ChatGPT explains
When asked about the accuracy of the references provided, ChatGPT gave varying answers. In one case, it claimed, “References are available in Pubmed,” and provided a web link. This link referred to other publications unrelated to the question. At another point, the software replied, “I strive to provide the most accurate and up-to-date information available to me, but errors or inaccuracies can occur.”
Despite even the most ‘truthful’ of these responses, ChatGPT poses hidden risks to academic, the researcher say.
“The importance of proper referencing in science is undeniable. The quality and breadth of the references provided in authentic studies demonstrate that the researchers have performed a complete literature review and are knowledgeable about the topic. This process enables the integration of findings in the context of previous work, a fundamental aspect of medical research advancement. Failing to provide references is one thing but creating fake references would be considered fraudulent for researchers,” says Dr Esli Osmanlliu, emergency physician at the Montreal Children’s Hospital and scientist with the Child Health and Human Development Program at the Research Institute of the McGill University Health Centre.
“Researchers using ChatGPT may be misled by false information because clear, seemingly coherent and stylistically appealing references can conceal poor content quality,” adds Dr Osmanlliu.
This is the first study to assess the quality and accuracy of references provided by ChatGPT, the researchers point out.
The Select Committee on Health and Social Services has extended the deadline for public comments on the contentious National Health Insurance (NHI) Bill by two weeks, according to a report from Business Insider. In its announcement, the Committee said that it had received numerous requests from stakeholders to extend the date on written submissions for the act.
The committee has therefore extended the deadline from Friday, 1 September 2023 to Friday, 15 September 2023. The Bill is already before the National Council of Provinces (NCOP) after being passed by Parliament in June, in spite of vehement opposition. Once past the NCOP, which seems all but assured given its stubborn progress, it will then be sent to President Cyril Ramaphosa to be signed into law.
Contact details to submit enquiries or written submissions are at the end of the article.
Controversy continues unabated
An unrelenting barrage of criticism has been directed at the Bill, which so far has shown little change in response and according to many its constitutionality is questionable. While stakeholders are generally for universal healthcare and the idea of an NHI, the current public healthcare system is already under dire pressure, being underfunded, under-resourced in terms of skilled professionals and equipment, and riddled with corruption.
Indeed, South Africa would be the first country in the world to completely bring all healthcare. The fact that other countries with better governance track records and more resources have not done so has been brought up as a red flag.
Another is the vague notion that the government will pay for the scheme somehow – which inevitably means reaching into taxpayers’ wallets. The estimated cost of R300 billion and R660 billion a year will be by far the largest single government expense in a time of shrinking funds.
“Looking at 2026 – the year in which the NHI is supposed to be implemented – an enormous extra R296 billion will be required in order to balance the books,” the Solidarity Research Institute (SRI) said.
“This is unheard of for a middle-income country, where spending on education usually enjoys the highest priority. While more affluent countries spend more on healthcare, social grants usually receive the highest priority, never health,” said the SRI.
Options to foot the bill range from a staggering 40% surcharge on income tax to a payroll tax of 13.4%, which Professor Alex van den Heever criticised as being “incredibly naïve set of fiscal proposals that you cannot even consider implementing.” Discovery Health CEO Ryan Noach warned of a tax revolt if the government attempts to pay for this.
Practical allternatives on offer include a public-private partnership as envisaged by Business Leadership South Africa CEO Busi Mavuso.
Enquiries, as well as written submissions, can be directed to Ms M Williams, Select Committee on Health and Social Services, e-mail mawilliams@parliament.gov.za.
Surgeons at NYU Langone Health have transplanted a genetically engineered pig kidney that continues to function well after 32 days in a man declared dead by neurologic criteria and maintained with a beating heart on ventilator support. This represents the longest period that a gene-edited pig kidney has functioned in a human, and the latest step toward the advent of an alternate, sustainable supply of organs for transplant.
Led by Robert Montgomery, MD, DPhil, the procedure was performed on July 24, 2023 and marks the fifth xenotransplant performed at NYU Langone. Observation is ongoing and the study will continue through mid-September 2023.
“This work demonstrates a pig kidney – with only one genetic modification and without experimental medications or devices – can replace the function of a human kidney for at least 32 days without being rejected,” said Dr Montgomery, who had previously performed the world’s first genetically modified pig kidney transplant into a human decedent in 2021.
Removing single troublesome gene
The first hurdle to overcome in xenotransplants is preventing so-called hyperacute rejection, which typically occurs just minutes after an animal organ is connected to the human circulatory system. By “knocking out” the gene that encodes the biomolecule known as alpha-gal, responsible for a rapid antibody-mediated rejection of pig organs by humans, immediate rejection has been avoided in all five xenotransplants at NYU Langone. Additionally, the pig’s thymus gland, which is responsible for educating the immune system, was embedded underneath the outer layer of the kidney to stave off novel, delayed immune responses. The combination of modifications has been shown to prevent rejection of the organ while preserving kidney function.
To ensure the body’s kidney function was sustained solely by the pig kidney, both of the transplant recipient’s native kidneys were surgically removed. One pig kidney was then transplanted and started producing urine immediately without any signs of hyperacute rejection. During the observation phase, intensive care clinical staff maintained the decedent on support while the pig kidney’s performance was monitored and sampled with weekly biopsies. Levels of creatinine, a bodily waste product found in the blood and an indicator of kidney function, were in the optimal range during the length of the study, and there was no evidence on biopsy of rejection.
The surgery was the latest in a larger study approved by a specific research ethics oversight board at NYU Langone and was performed after consultation with the New York State Department of Health. This important research, which study leaders say could save many lives in the future, was made possible by the family of a 57-year-old male who elected to donate his body after a brain death declaration and a circumstance in which his organs or tissues were not suitable for transplant.
A big leap toward a new organ source
“There are simply not enough organs available for everyone who needs one,” said Dr Montgomery, who received a hepatitis C-positive heart transplant himself in 2018. “Too many people are dying because of the lack of available organs, and I strongly believe xenotransplantation is a viable way to change that.”
The kidney and thymus gland used in this procedure were procured from a GalSafeTM pig, an animal engineered by Revivicor, Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) approved the GalSafe pig as a potential source for human therapeutics as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite.
Less may be more
While previous genetically engineered pig organ transplants have incorporated up to 10 genetic modifications, this latest study shows that a single-gene knockout pig kidney can still perform optimally for at least 32 days without rejection.
“We’ve now gathered more evidence to show that, at least in kidneys, just eliminating the gene that triggers a hyperacute rejection may be enough along with clinically approved immunosuppressive drugs to successfully manage the transplant in a human for optimal performance – potentially in the long-term,” said Dr Montgomery.
The NYU Langone team used standard transplant immunosuppression medications combined with enhanced screening of porcine cytomegalovirus (pCMV) in the donor pig to ensure safety. Recent studies have shown pCMV may affect organ performance and potentially trigger organ failure. No pCMV was detected after 32 days, and close surveillance of porcine endogenous retrovirus (PERV), along with six other viruses of interest, was performed.
Next steps
Monitoring of the pig kidney recipient will continue for another month with permission from the family, ethics committee approval and continued support from United Therapeutics. The additional data from the next several weeks will be analyzed further to develop a deeper understanding of this unique medical advance.
“We think using a pig already deemed safe by the FDA in combination with what we have found in our xenotransplantation research so far, gets us closer to the clinical trial phase,” said Dr Montgomery. “We know this has the potential to save thousands of lives, but we want to ensure the utmost safety and care as we move forward.”
Various stakeholders within the medical schemes value chain have sharply raised concerns over the unending court challenges brought by the Board of Healthcare Funders (BHF) against CMS. As an agile regulator, the CMS endeavours to clarify any misconception and confusion over BHF’s court challenges.
Chronology of Events
Initially, the main issue brought by BHF in this case was to request the court to grant them a general exemption for medical schemes to offer low-cost benefit options and to declare an alleged moratorium unlawful by the CMS and Ministry of Health in order to prevent medical schemes from offering low-cost benefit options.
In response, the CMS vehemently opposed the application on the basis that there was no moratorium as alleged by BHF and it would be thus unlawful to grant BHF a general exemption for medical schemes to offer low costs benefit options.
“It must be noted that while the main case/dispute was still ongoing (even after CMS submitted an extensive record of documents that were compliant with relevant information and documents having been exchanged between CMS and BHF), surprisingly BHF brought an interlocutory application alleging that CMS and the Minister were hiding certain information.”
Accordingly, the interlocutory application requested CMS and the NDOH to release an exhaustive list of documents which the CMS believed were irrelevant and had no bearing on the main application.
Despite CMS’s vehement contestation to the court on the additional requested documents by BHF, Judge Botha granted the BHF the order they sought, and the CMS, as well as the Minister of Health were ordered to produce the documents listed in Notice in terms of Rule 30A within 10 (ten) days of the Court Order, being 24 July 2023.
Before the expiration of rule 18 of the superior court, CMS filed leave to appeal the court order of Judge Botha as CMS believed that the order was flawed in law and that the judge had no reasons for ordering CMS and the Minister to produce those documents.
While the CMS legal team was studying the order, BHF concurrently lodged a contempt of court on an urgent basis.
CMS, through its attorneys, moved swiftly and wrote to BHF urging them to withdraw the contempt application as the CMS had already lodged its leave to appeal the court order of Judge Botha and this meant that the court order by Judge Botha would been suspended.
BHF refused to withdraw the contempt application and the application was heard on 8th August 2023 and the court dismissed BHF’s application on 10 August 2023 with costs in favour of CMS and Minister.
Citing Judge E van der Schyff who emphasised that “in the Practice Manual of the Gauteng High Court Division that while an application maybe urgent, it may not be sufficiently urgent to be heard at the time selected by an applicant” and also strongly highlighted that it does “not mean that applicants can indiscriminately approach the urgent court on the basis of extreme urgency without having regard to the context and facts of each individual application.”
Based on this order, the contempt application is now in our view moot or rather has been overtaken by the leave to appeal lodged by CMS and the Minister and CMS/NDOH. The leave to appeal will be heard somewhere September 2023.
The main application brought by BHF is likely to be heard in later parts of 2024.
