Systemic mastocytosis (SM) is a rare haematologic disorder that can lead to a range of debilitating symptoms across multiple organ systems and a significant impact on patients’ quality of life, and now the first medicine has been approved to specifically treat the most common form of the disease. On Monday 22 May, the US Food and Drug Administration (FDA) approved AYVAKIT® (avapritinib) to treat indolent systemic mastocytosis (ISM) in adults.
ISM represents the vast majority of SM cases, and AYVAKIT is now available for adults with ISM at the recommended dose of 25mg once daily. AYVAKIT was designed to potently and selectively inhibit KIT D816V, the primary underlying driver of the disease. AYVAKIT has been FDA approved for the treatment of advanced SM since June 2021.
“After decades of caring for people with indolent systemic mastocytosis, I have seen firsthand its profound impact on patients’ underlying mast cell burden, symptoms, physical and mental health, and ability to work and participate in daily activities,” said investigator Cem Akin, MD, PhD, Professor of Medicine at the University of Michigan. “Despite the use of multiple supportive care treatments, a considerable number of patients with indolent systemic mastocytosis continue to experience a substantial disease burden. AYVAKIT advances the treatment of indolent systemic mastocytosis by targeting KIT D816V, the primary underlying cause of the disease, and establishes a new standard of care for a broad population of patients with this disorder. AYVAKIT delivered statistically significant and consistent clinical improvements in the PIONEER trial, and based on these practice-changing data, I feel a tremendous sense of hope for the future for all those affected by the disease.”
The approval of AYVAKIT in ISM is based on data from the double-blind, placebo-controlled PIONEER trial – the largest study ever conducted for this disease – in which patients received AYVAKIT 25mg once daily plus best supportive care (AYVAKIT) or placebo plus best supportive care (placebo). AYVAKIT demonstrated significant improvements versus placebo in the primary and all key secondary endpoints, including overall symptoms and measures of mast cell burden.
AYVAKIT was well-tolerated with a favourable safety profile compared to placebo, and most adverse reactions were mild to moderate in severity. The most common adverse reactions for AYVAKIT (≥10%) were eye oedema, dizziness, peripheral oedema and flushing. Serious adverse reactions and discontinuations due to adverse reactions occurred in less than 1% of patients.
Detailed results from the PIONEER trial, including open-label extension study data showing the clinical benefits of AYVAKIT through 48 weeks of treatment, were presented in February 2023 at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.
Millions of doses of the Pfizer-BioNtech COVID-19 vaccine procured by the South African government have expired and the shot is largely unavailable to people in the country.
Several people who have contacted Spotlight have expressed “frustration” and “dismay” that despite government having announced in February that it was sitting on a massive stockpile of almost 30 million vaccines, they are struggling to access the Pfizer shot.
Explaining the vast quantity of unused vaccines, the Health Department at the time said vaccine uptake has been low due to decreasing cases, people’s erroneous perception that the pandemic is over, and hesitancy affected by vaccine disinformation.
Expired but not expired?
National Department of Health spokesperson Foster Mohale confirmed that seven million Pfizer doses had expired but they would not be disposed of. Instead, the vaccine manufacturers would test the vaccines to ensure continued safety and efficacy. The South African Health Products Regulatory Authority (SAHPRA) will review the test results and, if satisfied that the vaccine will still work as well as data showed before, they will approve an extended shelf life.
The remaining estimated 23 million Johnson and Johnson (J&J) vaccine doses in South Africa are due to expire in 2024 and 2025.
“The expiry of a vaccine is not the same as the expiry date of food which cannot be extended,” Mohale says, adding that the Pfizer vaccine has a short shelf life and that the vaccine’s expiry date has been extended twice in the past. He says the testing should be done by June and the Pfizer shots would become available in July.
Photo by Mat Napo on Unsplash
A mother from East London, who is hoping to emigrate to the United States, told Spotlight that she was “frantically” trying to get shots for her 12-year-old son in time to leave. In South Africa, none of the currently available COVID-19 vaccines have been authorised for use in children under the age of 16. Elsewhere in the world, for example, in the United States, the Pfizer vaccine has been tested and authorised for use for children from the age of 12. “It is mandatory that he get the vaccine before entering the United States,” she says.
An intern responding to people’s questions on the Department of Health’s hotline says, “Many callers have phoned in stressing about travelling, emigrating, or getting vaccinated for the first time. We have been told that there are very few sites that still have some stock. If people have had two Pfizer doses, they can boost with a J&J dose. However, if they have only had one Pfizer, they will have to wait.”
The public exasperation expressed directly to Spotlight and on social media also relates to the health department’s vaccination website being outdated and it being hard to find places to get vaccinated. As GroundUp reported in January, getting a COVID-19 booster jab is not as easy as it should be.
‘The pandemic is not over’
Referring to the World Health Organization’s (WHO) lifting of the COVID-19 Public Health Emergency of International Concern(PHEIC) on May 5th, Mohale says, “The pandemic is not over and people, especially those who are at highest risk of severe disease and death should get vaccinated.” These included people with co-morbidities and the elderly. He says vaccination for COVID-19 has been integrated into routine primary healthcare facilities, which is where people should go for their jabs.
WHO director-general Tedros Ghebreyesus said it was the end of the emergency phase but not the end of the threat of COVID-19. In the week prior to the announcement, he said the disease claimed a life (globally) every three minutes, “and that’s just the deaths we know about”.
The decision to lift the emergency was based on the decreasing number of deaths and hospitalisations from COVID-19, the high levels of population immunity against SARS-CoV-2, and the widespread availability of COVID-19 vaccines and treatments.
Ghebreyesus warned that the COVID-19 pandemic is not over and that the virus could still pose a serious threat to public health. The WHO has urged countries to continue to monitor the situation closely and to maintain preparedness measures, such as surveillance, testing, and contact tracing.
Some experts have criticised the WHO’s decision to end the emergency phase, arguing that it is premature and could lead to a resurgence of the pandemic. Others have defended the decision, arguing that it is based on the best available evidence and that it is important to give countries the flexibility to manage the pandemic in a way that best suits their own circumstances.
‘Momentous’ announcement
Professor Salim Abdool Kariem, Director of CAPRISA, described the announcement as “momentous”. Writing in his regular COVID-19 updates blog, he says, “… we are still living in the midst of a pandemic with thousands of cases each day. Since SARS-CoV-2 is going to be with us for a long time, a pragmatic decision was needed as the COVID-19 pandemic emergency has been steadily receding and a new variant of concern has not emerged in the last 17 months. But the risk of a new variant of concern is ever-present, even if it is getting progressively smaller with time. The public is also tired of the pandemic and many have simply put it out of sight and out of mind.”
Kariem writes that globally there are currently far more COVID-19 cases, hospitalisations, and deaths each day than we had on the day (30 January 2020) that COVID-19 was initially declared a PHEIC. “So, it (the WHO decision) was not based on the situation getting to a point pre-PHEIC. Waiting to reach that point may take many years or may never happen and so ending the PHEIC is a judgement call, taking many factors into consideration.”
‘Still with us’
Speaking at a recent webinar, hosted by Internews, science writer David Quammen, who wrote a book on COVID-19 called ‘Breathless: The Scientific Race to Defeat a Deadly Virus’ and before that, ‘Spillover’, says, “The coronavirus is still with us, it’s circulating worldwide among humans, and circulating also among whitetail deer, feral mink, and probably other wild mammals.”
He says efforts currently need to be directed to approaching COVID-19 as a long-term cause of human illness, suffering, and death, not “a short-term catastrophe”.
He says laboratory techniques need to be improved as well as manufacturing capacity for updated COVID-19 vaccines. Inequitable access to vaccines will need to be solved. “We will need to dissolve vaccine reluctance and refusal – among the privileged but obdurate, and also among those historically ill-served by Western medicine – with better communication and education.” Diagnostic testing needs to be maintained and not reduced, as well as the sequencing of genomes from patient samples to detect and trace new and immune-evasive variants, he says.
“We will need to prepare, not just for the next coming of SARS-CoV-2 (when it emerges from some infected human, or some deer or mink) but also for the next coronavirus or influenza virus (more than likely H1N1) or other highly adaptive animal-borne virus (there’s a whole rogue’s list of possibilities) that appears in humans, seemingly out of nowhere,” he says. “But they don’t come out of nowhere. They come from nature.”
Sacubitril/valsartan leads to greater reduction in plasma NT-proBNP levels compared to valsartan alone after stabilisation for worsening heart failure (HF) in patients with an ejection fraction (EF) above 40%, according to late breaking science presented today at Heart Failure 2023, a scientific congress of the European Society of Cardiology (ESC), and published in the Journal of the American College of Cardiology.
Principal investigator Dr Robert Mentz of Duke University Medical Center, Durham, US said: “These data add to the evidence supporting a potential treatment benefit of sacubitril/valsartan in patients with EF over 40% and particularly in those with EF below normal (< 60%). The findings may influence future guidance for the use of the drug in this population, both in and out of hospital and for those with acute, chronic or de novo heart failure.”
Guidelines recommend consideration of sacubitril/valsartan to reduce hospitalisations in patients with HF with preserved EF (HFpEF; EF >50%) and/or mildly reduced EF (HFmrEF; EF 41–49%). Recommendations differ around the world, with some noting benefits are more evident in those with EF on the lower end of this spectrum (ie below normal).
The PARAGON-HF trial excluded patients with decompensated heart failure, but a post-hoc analysis suggested a larger benefit with sacubitril/valsartan in those recently hospitalised. Whether initiation of sacubitril/valsartan is safe and effective in patients with EF over 40% stabilised after a worsening HF event was unknown. In addition, further data were needed in populations excluded by PARAGON-HF (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2, systolic blood pressure < 110mmHg, and body mass index [BMI] > 40kg/m2).
PARAGLIDE-HF evaluated the effect of sacubitril/valsartan versus valsartan on changes in NT-proBNP, safety and tolerability in HF patients with EF above 40% who had been stabilised after a worsening HF event. The primary endpoint was the time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. It was chosen to mirror the PIONEER-HF trial, which found that among patients with heart failure with reduced EF (< 40%) who were hospitalised for acute decompensated HF, sacubitril/valsartan led to a greater reduction in NT-proBNP concentration than enalapril.
Patients were recruited from 100 sites in the US and Canada. A total of 466 patients with EF above 40% were enrolled within 30 days of a worsening heart failure event (69% were enrolled while in hospital). The average age was 70 years, 52% were women and 22% were Black. Participants were randomly allocated in a 1:1 ratio to sacubitril/valsartan or valsartan. The time-averaged reduction in NT-proBNP was greater with sacubitril/valsartan compared with valsartan (ratio of change 0.85; p=0.049).
The secondary composite hierarchical outcome consisted of a) time to cardiovascular death, b)number and timing of HF hospitalisations, c) number and timing of urgent HF visits and d) time averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8. This outcome was evaluated using a win ratio analysis, which considers the clinical hierarchy and timing of each component of the endpoint. More serious events are given a higher priority and are analysed first. The hierarchical outcome favoured sacubitril/valsartan (as did each of the components) but was not significant (unmatched win ratio 1.19; 95% CI 0.93–1.52; p=0.16).
Regarding other secondary endpoints, compared with valsartan, sacubitril/valsartan reduced worsening renal function (odds ratio [OR] 0.61). There was more symptomatic hypotension in the sacubitril/valsartan group (OR 1.73). Importantly, subgroup analyses showed evidence of a larger treatment effect in those with EF ≤60% for the change in NT-proBNP (0.78) and the hierarchical outcome (win ratio 1.46).
Dr Mentz said: “PARAGLIDE-HF complements PARAGON-HF by focusing on patients stabilised after a worsening heart failure event with EF above 40% similar to the manner in which PIONEER-HF complemented PARADIGM-HF in patients with reduced EF. PARAGLIDE-HF had no run-in period, allowed both newly diagnosed heart failure and improved EF, included those with acute heart failure without specific echocardiographic requirements and overall had a diverse study population (52% women, 22% Black individuals). The trial also permitted patients with eGFR down to 20 mL/min/1.73m2, systolic blood pressure as low as 100mmHg, and any BMI. The broad and diverse population included in PARAGLIDE-HF supports the generalisability of these data to similar patients seen in routine practice.”
The Bacillus Calmette-Guérin (BCG) for tuberculosis vaccine has a number additional beneficial effects, and is currently a recommended therapy for non–muscle-invasive bladder cancer. In a new study published in JAMA Network Open, treatment with the BCG vaccine was associated with a reduced risk of Alzheimer’s disease and related dementias.
Although previous research has suggested a link between the BCG vaccine and a lower risk of dementia, studies were limited by size, study design, or analytical methods. To conduct a more robust study, researchers followed 6467 individuals for up to 15 years after they were diagnosed with non–muscle-invasive bladder cancer.
The group included 3388 patients who underwent BCG vaccine treatment and 3079 who served as controls, matched by factors such as age, sex, and medical co-morbidities.
During follow-up, 202 patients in the BCG vaccine group and 262 in the control group developed Alzheimer’s disease and related dementias. The incidence was 8.8 per 1000 person-years and 12.1 per 1000 person-years in the respective groups.
Analyses revealed that treatment with the BCG vaccine was associated with a 20% lower risk of Alzheimer’s disease and related dementias. The protective association was greater in patients aged 70 years or older. Additionally, during follow-up, 751 patients in the BCG vaccine group and 973 in the control group died. Thus, treatment with BCG vaccine was associated with a 25% lower risk of death.
Study leader Marc Weinberg, MD, Ph.D., an Instructor in Psychiatry at MGH, said: “A vaccine like BCG, if proven effective, is a perfect example of a cost-effective, population-health–based solution to a devastating illness like Alzheimer’s disease. We are shifting our focus towards studying the potential benefits of BCG vaccination of older adults in Alzheimer’s disease–related clinical trials.”
If a causal link is found, it will be important to understand the mechanisms involved. Weinberg and his colleagues note that the BCG vaccine’s effects on the immune system may play a role.
Researchers have developed a new method that combines palmitoleic acid, gentamicin, and non-invasive ultrasound to help improve drug delivery in chronic wounds that have been infected with Staphylococcus aureus and protected by thick biofilms. Their results were published in Cell Chemical Biology.
Chronic wounds are notoriously challenging to treat because of bacterial infections like S. aureus, which can also be resistant to antibiotics.
To defend itself from the immune system and other threats, S. aureus can band together, creating a slick, slimy biofilm around itself. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate through and neutralise the harmful bacteria.
Using a new strategy, researchers at the UNC School of Medicine and the UNC-NC State Joint Department of Biomedical Engineering were able to reduce the challenging MRSA infection in the wounds of diabetic mice by 94%. They were able to completely sterilise the wounds in several of the mice, and the rest had significantly reduced bacterial burden.
“When bacteria are not completely cleared from chronic wounds, it puts the patient at high risk for the infection recurring or of developing a secondary infection,” said senior author Sarah Rowe-Conlon, PhD. “This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients. We are excited about the potential of translating this to the clinic, and that’s what we’re exploring right now.”
Biofilms act as a physical barrier to many classes of antibiotics. Virginie Papadopoulou, PhD, was curious to know if non-invasive cavitation-enhanced ultrasound could create enough agitation to form open spaces in the biofilm to facilitate drug-delivery.
Liquid droplets which can be activated by ultrasound, called phase change contrast agent (PCCA), are applied topically to the wound. An ultrasound transducer is focused on the wound and turned on, causing the liquid inside the droplets to expand and turn into microscopic gas-filled microbubbles, when then move rapidly.
The oscillation of these microbubbles agitates the biofilm, both mechanically disrupting it as well as increasing fluid flow. Ultimately, the combination of the biofilm disruption and the increased permeation of the drugs through the biofilm allowed the drugs to come in and kill the bacterial biofilm with very high efficiency.
“Microbubbles and phase change contrast agents act as local amplifiers of ultrasound energy, allowing us to precisely target wounds and areas of the body to achieve therapeutic outcomes not possible with standard ultrasound,” said Dayton. “We hope to be able to use similar technologies to locally delivery chemotherapeutics to stubborn tumours or drive new genetic material into damaged cells as well.”
When the bacterial cells are trapped inside the biofilm, they are left with little access to nutrients and oxygen. To conserve their resources and energy, they transition into a dormant or sleepy state. The bacteria, which are known as persister cells in this state, are extremely resistant to antibiotics.
Researchers chose gentamicin, a topical antibiotic typically ineffective against S. aureus due to widespread antibiotic resistance and poor activity against persister cells. The researchers also introduced a novel antibiotic adjuvant, palmitoleic acid, to their models.
Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body that has strong antibacterial properties. The fatty acid embeds itself into the membrane of bacterial cells, and the authors discovered that it facilitates the antibiotic’s successful entry into S. aureus cells and is able to kill persistent cells and reverse antibiotic resistance.
Overall, the team is enthusiastic about the new topical, non-invasive approach because it may give scientists and doctors more tools to combat antibiotic resistance and to lessen the serious adverse effects of taking oral antibiotics.
“Systemic antibiotics, such as oral or IV, work very well, but there’s often a large risk associated with them such as toxicity, wiping out gut microflora and C. difficile infection,” said Rowe-Conlon. “Using this system, we are able to make topical drugs work and they can be applied to the site of infection at very high concentrations, without the risks associated with systemic delivery.”
Results of a new clinical trial involving the injection of an oncolytic virus – a virus that targets and kills cancer cells – directly into the tumour, with intravenous immunotherapy shows great promise for patients with glioblastoma according to results published in Nature Medicine.
Drs Farshad Nassiri and Gelareh Zadeh, neurosurgeons at the University Health Network (UHN) in Toronto, found that this novel combination therapy can eradicate the tumour in select patients, with evidence of prolonged survival.
Investigative work by the authors also revealed a new genetic signature within tumour samples that has the potential to predict which patients with glioblastoma are most likely to respond to treatment.
“The initial clinical trial results are promising,” says Dr Zadeh. “We are cautiously optimistic about the long-term clinical benefits for patients.”
Glioblastoma is a notoriously difficult-to-treat primary brain cancer. Despite aggressive treatment, which typically involves surgical removal of the tumour and multiple chemotherapy drugs, the cancer often returns, at which point treatment options are limited.
Immune checkpoint inhibitors are effective treatments for a variety of cancers, but they have had limited success in treating recurrent glioblastoma. This novel therapy involves the combination of an oncolytic virus and immune checkpoint inhibition, using an anti-PD-1 antibody as a targeted immunotherapy.
First, the team zeroed in on the tumour using stereotactic techniques and injected the virus through a small hole and a purpose-built catheter. Then, patients received an anti-PD-1 antibody intravenously, every three weeks, starting one week after surgery.
“These drugs work by preventing cancer’s ability to evade the body’s natural immune response, so they have little benefit when the tumour is immunologically inactive – as is the case in glioblastoma,” explains Dr Zadeh.
“Oncolytic viruses can overcome this limitation by creating a more favourable tumour microenvironment, which then helps to boost anti-tumour immune responses.”
The combination of the oncolytic virus and immune-checkpoint inhibition results in a ‘double hit’ to tumours; the virus directly causes cancer cell death, but also stimulates local immune activity causing inflammation, leaving the cancer cells more vulnerable to targeted immunotherapy.
Dr Zadeh and colleagues evaluated the innovative therapy in 49 patients with recurrent disease, from 15 hospital sites across North America.
UHN, which is the largest research and teaching hospital in Canada and the only Canadian institution involved in the study, treated the majority of the patients enrolled in the trial.
The results show that this combination therapy is safe, well tolerated and prolongs patient survival. The therapy had no major unexpected adverse effects and yielded a median survival of 12.5 months – considerably longer than the six to eight months typically seen with existing therapies.
“We’re very encouraged by these results,” says Dr Farshad Nassiri, first author of the study and a senior neurosurgery resident at the University of Toronto. “Over half of our patients achieved a clinical benefit – stable disease or better – and we saw some remarkable responses with tumours shrinking, and some even disappearing completely. Three patients remain alive at 45, 48 and 60 months after starting the clinical trial.”
“The findings of the study are particularly meaningful as the patients in the trial did not have tumour resection at recurrence – only injection of the virus – which is a novel treatment approach for glioblastoma. So, it’s really remarkable to see these responses,” says Dr Zadeh.
“We believe the key to our success was delivering the virus directly into the tumour prior to using systemic immunotherapy. Our results clearly signal that this can be a safe and effective approach,” adds Dr Nassiri.
The team also performed experiments to define mutations, gene expression, and immune features of each patient’s tumour. They discovered key immune features which could eventually help clinicians predict treatment responses and understand the mechanisms of glioblastoma resistance.
“In general, the drugs that are used in cancer treatment do not work for every patient, but we believe there is a sub-population of glioblastoma patients that will respond well to this treatment,” says Dr Zadeh. “I believe this translational work, combining basic bench science and clinical trials, is key to moving personalised treatments for glioblastoma forward.”
This is one of the few clinical trials with favourable results for glioblastoma over the last decade, and it was truly a team effort.
“The trial would not have been possible without our incredible OR teams, research safety teams and researchers – including Dr Warren Mason and his team at Princess Margaret Cancer Centre – and our brave patients and their families. We’re also grateful to the Wilkins Family for providing the funds to enable us to complete trials that advance care for our patients,” says Dr Zadeh.
The next steps for the group are to test the effectiveness of the combination therapy against other treatments in a randomised clinical trial.
“We are encouraged by these results, but there is still a lot of work ahead of us,” says Dr Nassiri. “Our goal, as always, is to help our patients. That’s what motivates us to continue this research.”
Despite our understanding of nutrition expanding remarkably in recent times, few aspects of our diet continue to confuse and divide the experts like nitrate. For a long time nitrate has been viewed warily, with previous research showing it could potentially be linked to causing cancer.
However, subsequent research has revealed dietary nitrate also has various cardiovascular health benefits, which could help reduce the risk of related conditions such as heart disease, dementia and diabetes.
So, how can one dietary compound have such contrasting potential risks and benefits? Researchers set out to find out how and why nitrate such contrasting potential risks and benefits, publishing their findings in Trends in Food Science & Technology.
All about the source
Dr Catherine Bondonno led a review of nitrate research and says the key may lie in where it comes from.
“We get nitrate from three major dietary sources: meat, water and vegetables,” she said.
“Nitrate’s reputation as a health threat stems from 1970, when two studies showed it can form N-nitrosamines, which are highly carcinogenic in laboratory animals.
“However, no human studies have confirmed its potential dangers, and our clinical and observational studies support nitrate preventing cardiovascular disease if it’s sourced from vegetables.
“So the review looked to unpack all of that, identify new ways forward and ways that we can solve this puzzle, because it’s really time to address it: it’s been 50 years.”
Urgency required
Despite recent research indicating the source of nitrate may affect its health benefits and risks, current dietary guidelines relating to nitrate have been in place since the 1970s and don’t differentiate between nitrate from meat, vegetables and water.
Dr Bondonno said while the 1970s animal studies reported a small incidence of malignant tumours, there was evidence not all nitrates deserve to be “tarred with the same brush.”
“For instance, unlike meat and water-derived nitrate, nitrate-rich vegetables contain high levels of vitamin C and/or polyphenols that may inhibit formation of those harmful N-nitrosamines associated with cancer,” she said.
Dr Bondonno said it was vital more research was conducted so guidelines could be updated.
“The public are unlikely to listen to messages to increase intake of nitrate-rich vegetables, if they are concerned about a link between nitrate intake and cancer.”
However, she stressed while official guidelines hadn’t changed, the apparent benefits of nitrate had seen many people potentially put themselves at risk.
“We need to be sure nitrate-rich vegetables don’t actually have an increased risk of cancer if we consume a higher amount,” she said.
“High dosage nitrate supplements are already used to improve physical performance in sport, while vegetable nitrate extracts are being added to cured meat products with a “clean label” claim, purporting to be better for you.
“So we really need to get this right.”
What do we eat, then?
Given its divided experts in the field, Dr Bondonno said it’s understandable people may be confused as to whether nitrate is good or bad for them.
“They’re probably thinking, ‘If I can’t have a salad, what CAN I have?’,” she said.
Despite the debate, she said current evidence suggests people should aim to get their nitrate from vegetables — but there was no need to go overboard.
“Dark green, leafy vegetables and beetroot are good sources, our research shows one cup of raw, or half a cup cooked per day is enough to have the benefits on cardiovascular health,” she said.
“We know processed meat isn’t good for us and we should limit our intake, but whether it’s the nitrate in them that is causing the problem or something else, we don’t know.
“It just further emphasises the need to investigate dietary nitrate to clarify the message for people.
“The potential cancer link was raised 50 years ago; now it’s time to conduct an in-depth analysis to distinguish fact from fiction.”
The risk of dying after a heart attack is more than twice as high for women than it is for men, according to research presented at Heart Failure 2023, held by the European Society of Cardiology (ESC).
“Women of all ages who experience a myocardial infarction are at particularly high risk of a poor prognosis,” said study author Dr Mariana Martinho of Hospital Garcia de Orta. “These women need regular monitoring after their heart event, with strict control of blood pressure, cholesterol levels and diabetes, and referral to cardiac rehabilitation. Smoking levels are rising in young women and this should be tackled, along with promoting physical activity and healthy living.”
Previous studies have found that women with ST-elevation myocardial infarction (STEMI) have a worse prognosis during their hospital stay compared to men, and that this may be due to their older age, increased numbers of other conditions, and less use of stents (percutaneous coronary intervention; PCI) to open blocked arteries. This study compared short- and long-term outcomes after STEMI in women and men, and examined whether any sex differences were apparent in both premenopausal (55 years and under) and postmenopausal (over 55) women.
This was a retrospective observational study which enrolled consecutive patients admitted with STEMI and treated with PCI within 48 hours of symptom onset between 2010 and 2015. Adverse outcomes were defined as 30-day all-cause mortality, five-year all-cause mortality and five-year major adverse cardiovascular events (MACE; a composite of all-cause death, reinfarction, hospitalisation for heart failure and ischaemic stroke).
The study included 884 patients. The average age was 62 years and 27% were women. Women were older than men (average age 67 vs 60 years) and had higher rates of high blood pressure, diabetes and prior stroke. Men were more likely to be smokers and have coronary artery disease. The interval between symptoms and treatment with PCI did not differ between women and men overall, but women aged 55 and below had a significantly longer treatment delay after arriving at the hospital than their male peers (95 vs 80 minutes).
The researchers compared the risk of adverse outcomes between women and men after adjusting for factors that could influence the relationship including diabetes, high cholesterol, hypertension, coronary artery disease, heart failure, chronic kidney disease, peripheral artery disease, stroke and family history of coronary artery disease. At 30 days, 11.8% of women had died compared to 4.6% of men, for a hazard ratio (HR) of 2.76. At five years, nearly one-third of women (32.1%) had died versus 16.9% of men (HR 2.33). More than one-third of women (34.2%) experienced MACE within five years compared with 19.8% of men (HR 2.10).
Dr Martinho said: “Women had a two to three times higher likelihood of adverse outcomes than men in the short- and long-term even after adjusting for other conditions and despite receiving PCI within the same timeframe as men.”
The researchers conducted a further analysis in which they matched men and women according to risk factors for cardiovascular disease including hypertension, diabetes, high cholesterol and smoking. Adverse outcomes were then compared between matched men and women aged 55 years and under, and between matched men and women over 55 years old.
There were 435 patients in the matched analysis. In matched patients over 55 years of age, all adverse outcomes measured were more common in women than men. Some 11.3% of women died within 30 days compared with 3.0% of men, for an HR of 3.85. At five years, one-third of women (32.9%) had died compared with 15.8% of men (HR 2.35) and more than one-third of women (34.1%) had experienced MACE compared with 17.6% of men (HR 2.15). In matched patients aged 55 years and below, one in five women (20.0%) experienced MACE within five years compared to 5.8% of men (HR 3.91), while there were no differences between women and men in all-cause mortality at 30 days or five years.
Dr Martinho said: “Postmenopausal women had worse short- and long-term outcomes after myocardial infarction than men of similar age. Premenopausal women had similar short-term mortality but a poorer prognosis in the long-term compared with their male counterparts. While our study did not examine the reasons for these differences, atypical symptoms of myocardial infarction in women and genetic predisposition may play a role. We did not find any differences in the use of medications to lower blood pressure or lipid levels between women and men.”
She concluded: “The findings are another reminder of the need for greater awareness of the risks of heart disease in women. More research is required to understand why there is gender disparity in prognosis after myocardial infarction so that steps can be taken to close the gap in outcomes.”
Combat-related injuries to bone are common in military personnel and can lead to pain and disability. Results from a new study in the Journal of Bone and Mineral Research suggest that amputations for such injuries may negatively affect bone mass.
Traumatic amputation from combat injuries has the potential to lead to osteoporosis through not only systemic inflammation and hormonal changes but also altered loading. Although a documented long-term complication of lower limb amputation is osteoporosis, this is often observed in older less active subjects with comorbidities, thus it is unknown whether this is secondary to systemic changes or changes to the loading environment.
In the study of 575 male adult UK military personnel with combat-related traumatic injuries and 562 without such injuries, veterans who sustained traumatic amputations often had low bone density in the hip region. Changes in bone health appeared to be mechanically driven rather than systemic and were only evident in those with lower limb amputations.
“We hope these results will drive further research into ways to reverse bone mineral density changes,” said co-author Group Captain Alex Bennett, Defence Professor of Rehabilitation, Defence Medical Rehabilitation Centre. “We need to investigate the role of prosthetics and exercise in reversing bone mineral density loss to reduce the longer-term risk of hip fracture. Because systemic treatments like bisphosphonates are not indicated in this young population with bone mineral density loss, it is important to understand other ways to reduce their hip fracture risk.”
While HIV and tuberculosis (TB) rates in South Africa are slowly declining, indications are that rates of non-communicable diseases (NCDs) like hypertension and diabetes are on the rise. One response to this shift is to bring some of the strategies used in combatting HIV to NCDs.
Hypertension, more commonly known as high blood pressure, has been described as a “silent killer” because there are often no symptoms associated with having it. Hypertension is when someone’s blood pressure is consistently higher than normal, which can lead to a host of complications, including stroke, heart attack, and kidney disease. Someone’s risk of developing hypertension is influenced by a number of things, including lifestyle, genetics, age, and family history as well as conditions like diabetes. (Spotlight previously reported on the state of hypertension in South Africa.)
90-60-50
For much of the last decade, UNAIDS’s 90-90-90 targets have been central to how governments have kept track of their HIV responses. The first 90 measured the success of testing programmes, the second 90 measured the success of efforts to get people on to treatment, and the third 90 provided information on how well people are doing once on treatment.
South Africa’s National Strategic Plan (NSP) for the prevention and control of NCDs (2022-2027) sets out similar targets for hypertension and diabetes. As with HIV, the three hypertension indicators will paint a picture of how South Africa is doing on testing, getting people onto treatment, and finally how well people are doing once on treatment.
The hypertension targets are as follows:
90% of people over 18 will know whether they have raised blood pressure.
60% of people with raised blood pressure will receive interventions.
50% of people receiving interventions for hypertension will have controlled blood pressure levels.
Implementation will be key
Local experts interviewed by Spotlight agree that the NSP is a step in the right direction but are clear that much more will be needed.
Professor Brian Rayner, Emeritus Professor in the Division of Nephrology and Hypertension at the University of Cape Town, says he finds the NSP lacking in practical details of how the targets will be achieved. “I’d love for the government to have the plan for how they can achieve this and not another document actually… they need to actually say how are we going do this,” he says.
Professor Angela Woodiwiss of the School of Physiology at the University of the Witwatersrand, and member of the board of the Southern African Hypertension Society has similar concerns. She says the objectives and deliverables in the NSP are sound, but it is short on details when it comes to implementation.
Ways to address this, according to Woodiwiss, is to include “examples of cost-effective practical approaches such as the establishment of cardiovascular screening centres at all district clinics where measurements of blood pressure are done; monthly screening drives at community centres over weekends to increase accessibility to those that work during the week; [and] awareness campaigns at shopping centres”. Another suggestion is for awareness and education campaigns on hypertension to be conducted on media platforms like TV and radio.
“In order to reduce the burden of disease, this target needs to be raised. I would therefore suggest 90-80-70 as the proportions,” she adds.
Professor Andre Kengne, the director of NCD research at the South African Medical Research Council, who was also part of the planning committee for this version of the NSP, says the plan is only a starting point. “The plan says that these [NSP targets] are the entry point, so it’s going to be a catalyst,” he says. “That’s why we just need to start somewhere and then improve on that and again, I think that’s exactly the approach that the plan is taking, This is let’s start small but with the aim of actually progressing.”
Screening: 90% of people over 18 will know whether they have raised blood pressure
A major challenge with NCDs such as hypertension and diabetes is that we don’t have very good epidemiological data in South Africa. Experts referred Spotlight to data from two sources.
Kengne says that based on data collected by the NCD Risk Factor Collaboration, a global network of health scientists that provide data on NCDs, which he is part of, about 40% of adult men and about 42% of adult women in South Africa had hypertension in 2019. Only about 38.5% of men with hypertension were diagnosed at the time and 61.5% of women.
Woodiwiss cites data collected through ‘May Measure Month’ (MMM) South Africa, of where she is a principal investigator. MMM is a global campaign run by the International Society of Hypertension to raise awareness. She cites data collected from screenings conducted from 2017 to 2022.
“The proportion of hypertensive adults aware that they have hypertension ranged from 42.5 to 56.7%,” she says.
When looking at the South African population as a whole, Woodiwiss calculates that this means that only around 13.6 to 19.6% of all people over the age of 18 are aware of whether they have hypertension or not. “We, therefore, have a long way to go in order to achieve the target of 90% of all adults being aware of whether they have raised blood pressure or not,” she adds.
Whichever of the two data sources you look at, South Africa seems to fall well short of the 90% target.
To improve the country’s performance on this measure, experts interviewed by Spotlight agree that there needs to be greater awareness of hypertension (including the importance of checking your blood pressure regularly) and better opportunities for screening.
“There will be no other way of actually improving the numbers without screening people,” Kengne says.
“The current screening approach is essentially hospital-based, and it’s not even yet comprehensive. Meaning only those in contact with the health system are likely, for a proportion, to get their blood pressure measured and then eventually diagnosed with hypertension,” he explains. “The first focus is really to optimise that hospital-based screening, to make sure that everything is in place to measure the blood pressure of whoever gets in contact with the health system.”
Ultimately, Kengne suggests what is needed is to implement community-based approaches to blood pressure screening. One way to do this would be to couple HIV community screening efforts with hypertension screening. As well as to empower community healthcare workers to check blood pressure when doing household visits and then refer people with elevated blood pressure to clinics if needed.
“There need to be national awareness campaigns on TV and radio. These campaigns can be used to encourage individuals to have their blood pressure measured at free screening sites such as community centres, shopping malls, and university campuses as is done as part of the May Measure Month campaign,” Woodiwiss suggests. She adds that a celebrity ambassador would be a great asset for such campaigns.
Treatment: 60% of people with raised blood pressure will receive interventions
“About 85% of those [men] who are diagnosed [with hypertension] are on treatment. And in women it’s about 86%,” Kengne says.
He adds that this is where the NSP targets are maybe not as ambitious as they could be because when you look at the data in the context of everyone who has hypertension (not just those with diagnosed hypertension), only 33% of men and 53% of women are on treatment.
In Woodiwiss’s data, the proportion of hypertensive adults who were receiving medication for hypertension ranged from 36.1 to 49.2%.
Either way, both data sources suggest that one of the biggest challenges to getting people onto treatment is actually diagnosing them in the first place. There is a question, however, whether the health system will be able to cope with the increased treatment load should diagnosis improve.
Kengne suggests that facilities, specifically public health sector facilities, may not be able to cope with the increased demand. “We’re going to need to prepare the health system to cope with the high demand for hypertension care subsequent to increased screening,” he says.
He thinks task-shifting may be part of the solution. Task-shifting was critical to the scaling up of South Africa’s HIV treatment programme, for example, by allowing qualifying nurses to prescribe antiretroviral treatment. Similarly, more healthcare workers, including community healthcare workers, nurses, and field workers can be trained to screen for and treat hypertension.
Woodiwiss stresses the importance of education and awareness when it comes to treatment.
“To facilitate the participation of individuals in the management of their blood pressure, education, and awareness are paramount… An important aspect is to empower individuals to be part of the management of their blood pressure; to re-enforce that hypertension is a chronic problem that requires daily management; and to dispel any notions of stigmatisation due to having high blood pressure,” she says.
Another important practical step would be to reduce the pill burden on hypertension patients in the public sector, according to Rayner. While medication is relatively cheap in this sector, there has not been a move towards combining multiple blood pressure drugs into a single pill, which would make patient adherence easier.
He adds that the process of prescribing blood pressure medication in the private sector needs to be simplified. In line with the idea of task-shifting, Rayner suggests allowing nurses to prescribe medication for straightforward hypertension cases in the public sector as a cost-effective way of treating hypertension.
Control: 50% of people receiving interventions are controlled
About 43% of men in South Africa with hypertension and who are on treatment have controlled blood pressure compared to 54.6% of women, according to Kengne. “Now taken as a proportion of all those with hypertension, I mean our target of 50% controlled will narrow down to about 27% of all people with hypertension [being controlled],” he says. “Using that as the estimate among men currently only 14% of all those with hypertension are controlled and among women, 29% are controlled.”
Data from Woodiwiss suggested that “the proportion of treated individuals with controlled blood pressure ranges from 49.6 to 57.5%.”
For this target then, the country isn’t too far off the 50% target.
But Kengne stresses that blood pressure control is not straightforward. “Diagnosing, it’s not that difficult. Starting treatment it’s not difficult, but actually treating to target it’s a challenge and a number of factors can come into play. Some factors [are] linked to people with hypertension [and] some linked to healthcare providers and the health system,” he says.
For patients, issues like adherence to treatment can be difficult. He suggests using mobile technology, like text messages, to remind patients to take their medication. As well as reducing the pill burden by investing in combination medications.
From the healthcare provider side, Kengne says there needs to be monitoring of patients so that changes to the treatment plan can be made if needed so that the patient can achieve blood pressure control.
“Improving the proportion of treated individuals who have controlled blood pressure requires ongoing monitoring and regular blood pressure checks. As the vast majority of South Africans cannot afford home blood pressure monitors, easy access to blood pressure checks at community clinics, pharmacies, etc. should be provided country-wide,” Woodiwiss says. “It would be ideal if companies could all have corporate wellness days for employees.”
