A new study of a brain region called the rostro-medial prefrontal could potentially advance diagnosis and therapies for Borderline Personality Disorder (BPD). Published in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, the research revealed that the rostro-medial prefrontal specifically becomes more active when people are rejected by others at greater rates. However, individuals with BPD – characterised by interpersonal sensitivity to rejection and emotional instability – do not display rostro-medial prefrontal cortex activity when rejected.
The brain reacts with rostro-medial prefrontal activity to rejection as if there is something “wrong” in the environment. This brain activity may activate an attempt to try to restore and maintain close social ties to survive and thrive. This region of the brain also is activated when humans try to understand other peoples’ behaviour in light of their mental and emotional state.
“Inactivity in the rostro-medial prefrontal cortex during rejection may explain why those with BPD are more sensitive and more distressed by rejection. Understanding why individuals with this debilitating and high risk disorder experience emotional distress to rejection goes awry will help us develop more targeted therapies for BPD,” said psychologist Eric A. Fertuck, associate professor at City College of New York.
On the significance of the study, Fertuck noted that while previous findings in this area have been mixed, “what we’ve done is improve the specificity and resolution of our rejection assessment, which improves on prior studies.”
Research continues with several investigations underway examining the role of social rejection in different mental health problems including post-traumatic stress disorder, depression, and social anxiety.
A massive and much-anticipated phase 3 trial of an experimental tuberculosis (TB) vaccine is set to proceed after funding for it has been secured from two large philanthropies. Wellcome and the Bill & Melinda Gates Foundation (BMGF) Wednesday announced they’d be investing a combined $550 million into the trial – around $150 million from Wellcome and the remaining from the Bill & Melinda Gates Medical Research Institute, a nonprofit subsidiary of the BMGF.
The vaccine, called M72/AS01E or just M72, made headlines in September 2018 when it was found to offer 54% protection against pulmonary TB disease in a phase 2B trial. That trial, of around 3 300 people, was conducted in South Africa, Zambia, and Kenya. Final results from that study were published in the New England Journal of Medicine in 2019 – efficacy in these final results was down to around 50%.
Medicines and vaccines are typically only brought to market once safety and efficacy have been confirmed in a large phase 3 trial. In this case, the phase 3 trial is set to have around eight times as many participants as the phase 2B trial.
26 000 study participants
“Conducted in collaboration with an international consortium of TB clinical investigators, the trial will enrol approximately 26 000 people, including people living with HIV and without TB infection, at more than 50 trial sites in Africa and Southeast Asia,” Wellcome and BMGF said in a statement announcing the trial.
They said the trial will “assess the candidate vaccine’s efficacy at preventing progression from latent TB infection to pulmonary TB”. In an online media conference on Wednesday Trevor Mundel, President for Global Health at BMGF, clarified that while most study participants will be people with latent TB infection, 4 000 people without TB infection would also be recruited. This is because establishing evidence of the vaccine’s safety in people without latent TB infection will be important if the vaccine is to be rolled out in areas with high background rates of TB without first having to test everyone for latent infection. “You’d want to be comfortable with vaccinating everyone in the community,” he said, “So we need to have that safety data in the uninfected as well in order to be able to have that usage, which will be the easiest way to use the vaccine at the end of the day.”
Mundel said that the study is scheduled to start early in 2024 and that it is expected to last for four to six years. Exactly how long the study will take will depend largely on how long it takes for 150 study participants to develop active TB – the number required for the study to have sufficient statistical power. By comparison, recruitment for the phase 2B trial started in 2014 and the first findings from that study were published in 2018.
According to the statement, additional details about the trial design and participants will be announced in the coming months.
Given that the phase 2B trial was partially conducted in South Africa and the country has substantial TB clinical trial capacity, it is almost certain that some of the 50 trial sites will be in South Africa – although know specific trial sites have yet been announced.
As pointed out in the statement, the only TB vaccine in use today, bacille Calmette-Guerin (BCG), was first given to people in 1921. It helps protect babies and young children against severe systemic forms of TB but offers limited protection against pulmonary TB among adolescents and adults. If the findings from the phase 3 trial of M72 are positive, m72 will become the first new TB vaccine in over a hundred years to be proven safe and effective.
According to the most recent figures from the World Health Organization (WHO), around 304 000 people fell ill with TB in South Africa in 2021. While TB rates are declining, they are declining relatively slowly and according to the most recent WHO World TB Report, a major technological breakthrough such as a new vaccine will be needed if ambitious TB control targets are to be met.
Announcement welcomed
“We’ve waited a long time for this study, so are happy to see the Bill & Melinda Gates Foundation and Wellcome taking up this important task,” said Patrick Agbassi, chair of the Global TB Community Advisory Board, in a comment included in the Wellcome/BMGF statement. “The question now becomes how we can enroll 26 000 people most quickly and ensure that all populations at risk of TB will ultimately be able to benefit from access to what could be the first new TB vaccine in over 100 years. A robust community engagement programme will be key, as will taking on studying this vaccine in younger adolescents, pregnant women, people with prior history of TB, and other key groups often underrepresented or left out entirely of TB trials and the benefits of scientific progress.”
Mark Harrington, executive director of New York-based advocacy organisation Treatment Action Group (TAG) said, “TAG welcomes this historic investment in TB vaccine development by Wellcome and the Bill & Melinda Gates Foundation. A Phase III clinical trial of the M72/AS01E TB vaccine candidate is a long-awaited milestone. We hope this funding commitment sparks governments and other funders to substantially increase investments in the TB vaccine pipeline, which contains a number of promising candidates in addition to M72/AS01E but faces a dire financial shortfall.”
“This Phase III trial,” Harrington said, “will take several years to complete. We encourage the Gates Foundation, Wellcome, GSK, country governments, and other partners to use this time to lay the groundwork for eventual vaccine adoption by ensuring the availability, affordability, and acceptability of M72/AS01E should it prove safe and effective.”
Initial development of M72 was driven by the pharmaceutical company GSK with support from several governments, philanthropies, and research organisations. The vaccine contains the M72 recombinant fusion protein, which the Wellcome/BMGF statement explains is derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A) combined with the GSK proprietary Adjuvant System AS01E. According to the statement, GSK will continue to provide the adjuvant for the vaccine’s further development and potential launch.
NOTES: (1) The BMGF is mentioned in this article. Spotlight receives funding from the BMGF, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council. (2) A representative of the Global TB Community Advisory Board is quoted in this article. Spotlight editor Marcus Low was previously a member of the Global TB Community Advisory Board.
Researchers in Japan have developed a new radiotherapy technique that has the potential to treat several kinds of cancer, with fewer negative side effects than currently available methods. Published in Chemical Science, the proof-of-concept study showed that tumours in mice grew almost three times less and survival was 100% after just one injection of an alpha-particle emitting radioisotope inside of cancer cells, killing them but sparing healthy tissue.
The side effects of standard chemotherapy and radiation treatment can be devastating, and the eradication of all cancer cells is not guaranteed, especially when the cancer has already metastasised and spread throughout the body. Therefore, the goal of most research these days is to find a way to specifically target cancer cells so that treatments only affect tumours. Some targeted treatments do exist, but they cannot be applied to all cancers. Researchers led by Katsunori Tanaka at the RIKEN Cluster for Pioneering Research (CPR) in Japan and Hiromitsu Haba at the RIKEN Nishina Center for Accelerator-Based Science (RNC) developed this new approach.
“One of the greatest advantages of our new method,” says Tanaka, “is that it can be used to treat many kinds of cancer without any targeting vectors, such as antibodies or peptides.”
The new technique relies on basic chemistry and the fact that a compound called acrolein accumulates in cancer cells. A few years ago, Tanaka’s team used a similar technique to detect individual breast cancer cells. They attached a fluorescent compound to a specific type of azide – an organic molecule with a group of three nitrogen atoms (N3) at the end. When the azide and acrolein meet inside a cancer cell, they react, and the fluorescent compound becomes anchored to structures inside the cancer cell. Because acrolein is almost absent from healthy cells, this technique acted like a probe to light up cancer cells in the body.
In the new study, rather than simply detecting cancer cells, the team targeted those cells for destruction. The logic was fairly simple. Instead of attaching the azide to a fluorescent compound, they attached it to something that can kill a cell without harming surrounding cells. The chose to work with astatine-211, a radionuclide that emits a small amount of radiation in the form of an alpha particle as it decays. Compared to other forms of radiation therapy, alpha particles are a little more deadly, but they can only travel about one twentieth of a millimetre and can be stopped by a piece of paper. In theory, when astatine-211 is anchored to the inside a cancer cell, the emitted alpha particles should damage the cancer cell, but not much beyond.
Once the team figured out the best way to attach astatine-211 to the azide probe, they were able to perform a proof-of-concept experiment to test their theory. They implanted human lung-tumour cells into mice and tested the treatment under three conditions: simply injecting astatine-211 into the tumour, injecting the astatine-211-azide probe into the tumour, and injecting the astatine-211-azide probe into the bloodstream. The found that without targeting, tumours continued to grow, and mice did not survive. As expected, when the azide probe was used, tumours grew almost three times less and many more mice survived – 100% when it was injected into the tumour and 80% when injected into the blood.
“We found that just one tumour injection with only 70kBq of radioactivity was extremely effective at targeting and eliminating tumour cells,” says Tanaka. “Even when injecting the treatment compound into the bloodstream, we were able to achieve similar results. This means we can use this method to treat very early-stage cancer even if we don’t know where the tumour is.” The fluorescent probe version of this technique is already being tested in clinical trials as a way of visualising and diagnosing cancer at the cellular level. The next step is to find a partner and begin clinical trials using this new method to treat cancer in humans.
The Passing of the National Health Insurance Bill on 12 June 2023 by parliament has many stakeholders in the healthcare industry concerned as to what the implications are. The reality is that there is a long and challenging process ahead, and the NHI Bill has many years to go before all of its provisions could be implemented.
Putting all the challenges and debate aside, Jacqui Nel, business unit head of healthcare at Aon South Africa, highlights the salient points that are at the heart of the matter. “First and foremost, I would like to affirm that the private healthcare sector needs to focus all its efforts on objectively collaborating with all parties concerned to achieve a stronger and affordable healthcare solution for all South Africans. The concept and ideals of providing universal health coverage should not be in dispute.”
“The overarching principle of the NHI bill is to provide universal health coverage and social solidarity, providing all citizens with access to the same essential health care benefits, regardless of their financial means,” she adds.
However, the road to successfully implementing NHI is a long and costly one, with many experts saying it can take up to 15 years to achieve, if not more. Purely from a legislative point of view, there are no less than 11 pieces of legislation that will need to be amended to align with NHI objectives, and this is an onerous process.
This includes:
National Health Act
Mental Health Care Act
Occupational Diseases in Mines and Works Act
Health Professions Act
Traditional Health Practitioners Act
Allied Health Professions Act
Dental Technicians Act
Medical Schemes Act
Medicines and Related Substances Act
Nursing Act
And various Provincial Health Acts.
The first of many court cases are already making headlines. “On the constitutional front, one of the 11 pieces of legislation requiring amendment is the National Health Act, which governs the ‘Certificate-of-Need’ (CoN), a piece of legislation that would dictate to private sector doctors where they are permitted to practice and what services they may provide. This ‘CON’ is essential to government to control doctors under the NHI plans and is being challenged by trade union Solidarity and six other parties,” says Nel.
About the NHI Bill
The NHI Bill lays out the duties and functions of the NHI Fund, which are primarily to strategically purchase health care services based on the principles of social solidarity. All permanent residents and citizens will be eligible as beneficiaries of the “Fund” as it is referred to; and temporary residents and foreigners will have access to emergency medical treatment and access to other health services as determined through a mandatory travel insurance.
“The Bill states that eligible beneficiaries will be able to access health services through registering as a user of the “Fund”. Each member will have a number that is unique to them and their dependents. The Fund will then reimburse health care providers directly for services rendered, provided they have met the accreditation requirements. It is envisaged that comprehensive health services benefits must be made available and these services will be determined by the Benefits Advisory Committee,” explains Nel.
The Bill also refers to the establishment of the ‘Board of the Fund’, and the remuneration and reimbursement of the members of the Board which will be determined by the Minister of Health in consultation with the Minister of Finance. “There are various other functions of the fund for which further administrative departments will need to be set up to address planning, benefits design, price determination, accreditation, purchasing and contracting, payments, procurements, performance monitoring and a risk and fraud prevention unit,” says Nel.
However, there are major points of concern that remain and will need to be addressed to facilitate any implementation of the NHI into South African society, which include:
Ministerial powers, good governance and accountability.
Role of the different spheres of government.
Role of medical schemes.
Tax implications for taxpayers, both from an employee and employer perspective.
NHI funding models – increased taxes?
Health financing expertise.
Training of healthcare providers – consequence management.
Service delivery at state facilities and healthcare facilities.
Infringement on the right of choice.
Lack of detail around major parts of the NHI Bill.
In summary, this Bill is the roadmap to NHI, but many other pieces of legislation will have to be amended, and a crucial element is currently still missing which is the cost of NHI and what the basket of services will include. “To enable the NHI will require an appropriation bill from National Treasury to detail how the NHI is going to be funded. However, detail on this has been slim, while government’s finances are heavily constrained and look likely to worsen in the future with various global and local factors coming into play,” says Nel.
“We fully expect that there are going to be significant challenges to the many technical and restrictive provisions contained within the NHI Bill, and these challenges may well alter its entire substance, and there is also the prospect of political shifts that could have a material impact on health policy going forward. We simply do not see any material shifts to the private healthcare sector anytime soon,” Nel explains.
What is certain is that the Bill in its current shape and format is unlikely to remain as it is today. “While the NHI Bill raises serious concerns, there is no disputing the need for structural change. There will be much debate and negotiation in the years ahead in unpacking the strengths and weaknesses of current public and private healthcare systems, and we look forward to a rational and workable solution to the achievement of better healthcare and to assist in a workable solution for all South Africans,” Nel concludes.
Taking higher-than-recommended doses of vitamin D for five years reduced the risk of atrial fibrillation in older adults, according to a randomised controlled study conducted in Finland and published in the American Heart Journal.
Atrial fibrillation is the most common arrhythmia, the risk of which increases with age, and which is associated with an increased risk of stroke, heart failure and mortality. Vitamin D has been shown to have an effect, for example, on the atrial structure and the electrical function of the heart, suggesting that vitamin D might prevent atrial fibrillation.
Conducted at the University of Eastern Finland in 2012–2018, the main objective of the Finnish Vitamin D Trial (FIND) was to explore the associations of vitamin D supplementation with the incidence of cardiovascular diseases and cancers. The five-year study involved 2 495 participants, men aged 60 and older, and women aged 65 and older, who were randomised into three groups: one placebo group and two vitamin D3 supplementation groups, with one of the groups taking a supplement of 40µg (1600 IU) per day, and the other a supplement of 80µg (3200 IU) per day. All participants were also allowed to take their personal vitamin D supplement, up to 20µg (800 IU) per day, which at the beginning of the study was the recommended dose for this age group. Participants had no diagnoses of cardiovascular disease or cancer at baseline, and they completed comprehensive health-related questionnaires, both at the beginning. Data on the occurrence of diseases and deaths were also obtained from Finnish nationwide health registers. Approximately 20% of participants were randomly selected for more detailed examinations and blood samples.
During the five-year study, 190 participants were diagnosed with atrial fibrillation: 76 in the placebo group, 59 in the 40µg group, and 55 in the 80 micrograms group. The risk of atrial fibrillation was 27% lower in the 40µg group, and 32% lower in the 80 micrograms group, when compared to the placebo group. In the sub-cohort selected for more detailed examinations, the mean baseline serum calcidiol concentration, which is a marker of the body’s vitamin D concentration, was relatively high, 75nmol/l. After one year, the mean calcidiol concentration was 100nmol/L in the 40µg group, and 120nmol/l in the 80µg group. No significant change in the calcidiol concentration was observed in the placebo group.
Only two randomised trials tried to test whether vitamin D supplementation reduces AF risk in healthy adults, and they did not observe an effect when using doses of 10µg (400 IU) or 50µg (2000 IU) per day. Further confirmation of the present results from the FIND study is therefore needed before doses of vitamin D that significantly exceed current recommendations can be recommended for preventing atrial fibrillation. The FIND study has previously published findings showing no association with the incidence of other cardiovascular events or cancers.
