Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. Studying this type of headache may provide new insights into the mechanisms behind headaches on Earth. The study was published in Neurology.
“Changes in gravity caused by space flight affect the function of many parts of the body, including the brain,” said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands.
“The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull.”
The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency. They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.
Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year.
None of them had a history of recurrent headaches or had ever been diagnosed with migraine.
Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3596 days in space for all participants. Astronauts completed health screenings and a questionnaire about their headache history before the flight.
During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.
The astronauts reported 378 headaches in flight. Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.
Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine. Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight.
During this time, 21 astronauts had one or more headaches for a total of 51 headaches – of which 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.
In the three months after return to Earth, none of the astronauts reported any headaches.
“Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth,” said Van Oosterhout.
“Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights.”
This research does not prove that going into space causes headaches; it only shows an association.
A limitation of the study was that astronauts reported their own symptoms, so they may not have remembered all the information accurately.
While three new tuberculosis (TB) medicines have been registered in South Africa over the last decade, TB treatment still comes with several side effects and requires taking multiple different medicines, typically for six or more months. The search for better TB medicines got a boost last week with the presentation of promising findings from a study conducted in South Africa on an experimental drug called quabodepistat. Elri Voigt reports on this and other TB studies presented at a conference in Denver, Colorado.
Arguably, the biggest TB news at the Conference on Retroviruses and Opportunistic Infections (CROI) this year was that the experimental new TB drug quabodepistat performed well in a phase 2b/c clinical trial. This means the drug can now proceed to a pivotal phase 3 trial (medicines are typically approved by regulators only after positive results in phase 3 trials).
The interim study results presented at CROI indicated that quabodepistat in combination with bedaquiline and delamanid and given for four months to people with drug susceptible TB is safe and efficacious, when compared to the six-month standard of care regimen. The standard of care regimen, currently used in South Africa’s public sector, consists of the drugs rifampicin, isoniazid, ethambutol, and pyrazinamide.
Participants were split into four study arms to either receive 10mg, 30mg or 90mg of quabodepistat (along with delamanid and bedaquline) once a day for four months or the standard of care regimen for six months. In the quabodepistat arms, a total of 98 study participants completed treatment, compared to 19 in the standard of care arm.
Taken together, 96% of participants in the quabodepistat arms had sputum culture conversion compared to 91% in the standard of care arm. Sputum culture conversion means TB was no longer detected in sputum samples that people coughed up when those samples were grown in the lab.
The study was conducted at several sites in South Africa and was funded by the Japanese pharmaceutical company Otsuka.
‘Furthest along’
Lindsay McKenna, the TB Project Co-Director at Treatment Action Group (TAG – a New York-based NGO), explained to Spotlight that quabodepistat is a new drug with a new mechanism of action for inhibiting TB’s cell wall synthesis. Essentially, this means that the drug interferes with the TB bacteria’s cell wall structure.
While there are a few new drugs that work the same way, quabodepistat is the furthest along.
“It’s the first in a new class of TB drugs to reach this stage since bedaquiline and delamanid were in phase 2b over ten years ago,” McKenna said.
There is however still some way to go before we will know if quabodepistat is bound for wider use than just in clinical trials. “We need to see data on clinical outcomes first,” McKenna told Spotlight, adding that quabodepistat is also being assessed in another ongoing phase 2b/c clinical trial.
“Remember that we have only seen sputum culture conversion results. Follow up is ongoing and so we will learn more when we see the proportion of participants with favorable outcomes (for example relapse free cure) 12 months post randomisation,” she said. “In the meantime, I think Otsuka should immediately begin working to start up a pre-approval access programme to enable people with unmet needs to access quabodepistat.”
Safety signals
Dr Simbarashe Takuva, Associate Director of Clinical Development at Otsuka Novel Products GmbH (an affiliate of Otsuka), who presented the results on behalf of the study team, said that overall, the quabodepistat regimen was well tolerated and considered safe.
In terms of side effects, the adverse events reported were generally described as mild or moderate, but there were some concerning signals. Grade 3 adverse events stood at 15% in the quabodepistat 10mg arm, 12% in the 30mg arm, 11% in the 90mg arm and 5% in the standard of care arm. Grade 3 adverse events are typically serious enough to prevent someone from working.
Takuva said that there were no serious adverse events (which we understand to mean grade 4/life threatening adverse events) related to the study drugs. There were also no treatment discontinuations related to the drugs. There was a single death in the study, a 25-year-old man who had met all study eligibility criteria but got sicker during the study. The study drugs were halted and standard of care drugs were given instead but the participant later died in hospital.
The researchers also looked for signs that quabodepistat might adversely affect the liver and the heart, but no safety signals related to the drugs were seen in either the liver (hepatoxicity) or the heart (cardiotoxicity).
“The data presented didn’t raise concerns about any treatment related cardio- or hepatotoxicity signals, however, it was a relatively small study, and the inclusion criteria were conservative,” McKenna commented on these findings.
One snag is that the results presented at CROI did not provide a clear answer regarding which of the three quabodepistat dosages in the study is preferable. Based on the clinical data, Takuva said it is difficult to determine which dose is best to use. He did however point out that additional work is being done looking at Pharmacokinetic and Pharmacodynamic data which will hopefully help provide more information on the ideal dose.
“Follow up on this study is ongoing. We await the final results of our phase 2 trial toward the end of the year,” he told Spotlight.
No study participants with HIV
One big limitation of these results is that the study did not enroll any people living with HIV. According to Takuva, the study had a strict exclusion criterion for the CD4 count of enrolling anyone living with HIV. A person’s CD4 count is a measure of the state of one’s immune system – higher counts are better.
Initially, the CD4 count cut off for the study was set at above 500 cells/mm3, then was amended to 350 cells/mm3 and finally it was dropped to above 250 cells/mm3 but by that time it was too late to enroll anyone living with HIV.
“The interim results are encouraging. However, I was really surprised and disappointed that they weren’t able to enroll any people living with HIV in the trial,” McKenna told Spotlight.
When asked about this, Takuva told Spotlight that the protocol did include the provision to recruit people living with HIV, but it was not feasible to include any. However, people living with HIV will be considered as important to include in any phase 3 trials going forward.
“As with all studies, we need to balance patient safety and the goal of the study outcome. In this instance, despite our best efforts, recruitment of people living with HIV was not feasible, though as we consider the possibility of a phase 3 trial, people living with HIV will remain a population that we consider important to include as far as possible in the phase 3 trial,” he said.
Treating DR-TB in people living with HIV
In contrast to the lack of people with HIV in the quabodepistat study, research was also presented at CROI looking specifically at how people living with HIV did in the landmark endTB trial. Other results from endTB were previously reported and the trial is widely considered one of a hand full of key trials transforming the treatment of drug-resistant forms of TB. The researchers found that two nine-month regimens studied in endTB did particularly well in people living with HIV. Such findings are of particular importance in a country like South Africa where many people who fall ill with TB are also living with HIV. (For those interested in the details, the two regimens were bedaquiline/linezolid/moxifloxacin/pyrazinamide and bedaquiline/clofazimine/linezolid/levofloxacin/pyrazinamide)
Some disappointments
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash
In a disappointing development, researchers presenting at CROI reported that a study testing a three-month regimen for the treatment of drug-susceptible TB was stopped early after an interim review found the regimen had poor efficacy compared to the six-month standard of care. The regimen contained the drugs clofazimine and rifapentine, among others. It means that for now the shortest regimen for treating drug-susceptible TB validated in a clinical trial remains a four-month regimen containing the medicines rifapentine and moxifloxacin, among others. That four-month regimen is not yet in wide use, even though findings confirming its safety and efficacy were reported in 2020.
We also received some bad news on an experimental TB vaccine called H56:IC31. The idea of H56:IC31 was to vaccinate people who were just cured of TB to prevent the TB from coming back – people whose TB is deemed to be cured are known to have an increased risk of falling ill with TB again. Despite promising signs in earlier studies, the vaccine failed to reduce TB recurrence in a phase 2 clinical trial of over 800 people. Much of this study was conducted at sites in South Africa.
TB treatment’s impact on mental and physical health
Another interesting study conducted in South Africa and presented at CROI looked at the changes in mental and physical health that people ill with TB experience before and after treatment. It found that the quality of life and physical fitness of participants was reduced at the start of TB treatment but did improve by the end of TB treatment.
The researchers looked at 200 study participants split between South Africa, Zambia, Malawi, Mozambique and Zimbabwe. Their mental and physical health was assessed when they started TB treatment through a standardised short form quality of life survey, depression assessed through a patient health questionnaire and their physical health was tested using a six-minute walk test. Participants were assessed again when treatment was completed, and data was compared to see what changed between the start and end of TB treatment.
Overall, participant’s physical quality of life increased by 39% by the end of TB treatment, mental quality of life increased by 19%, ability to do a six-minute walk increased by 15% and depression scores decreased by 26%.
Long-acting therapies for TB
Long-acting therapies have been making waves for some time in HIV treatment and a long-acting injection and ring are currently being offered in pilot projects in South Africa. Two studies of long-acting therapies in mice presented at CROI show that there is at least some movement in this area as well when it comes to TB. Such long-acting therapies have particular potential for TB preventive therapy – with for example what is now a three-month course of pills being administered as a single long-acting injection.
One study found that a long-acting injectable form of the drug rifapentine had similar efficacy to a one-month course of preventive therapy in pill form, while another had similarly promising findings for an injection using a long-acting formulation of a diarylquinoline (a class of TB drugs that include bedaquiline). It is anticipated these early proof of concept mouse studies will be followed by studies in humans.
A person’s age, sex and location are correlated with the chance that they have a bloodstream infection that is resistant to antibiotics, according to a new study published March 14th in PLOS Medicineby Gwenan Knight of the London School of Hygiene and Tropical Medicine, UK, and colleagues.
Antimicrobial resistance (AMR), in which infections cannot be treated with antibiotics, is a major global public health threat.
Little has been known about how the prevalence of resistance varies with age and sex even though antibiotic usage, changes in immune function, and exposure to high-risk settings are all linked to age and sex.
In the new study, researchers analyzed data collected as part of routine surveillance between 2015 and 2019 on bloodstream infections in 944,520 individuals across 29 European countries.
The team looked at which bacterial species were isolated and sent to the surveillance service, and which antibiotics were used to treat the infections.
Distinct patterns in resistance prevalence by age were observed throughout Europe but varied across bacterial species.
For most but not all bacteria, peaks in resistance were seen at the youngest and oldest ages.
The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) increased with age and the occurrence of aminopenicillin resistance in Escherichia coli decreased with age.
Some antimicrobial resistance profiles peaked in middle-age; Pseudomonas aeruginosa was most likely to be resistant to several antibiotics around 30 years of age and, for women, the incidence of bloodstream infections due to E. coli peaked between ages 15 and 40. There were other important differences between sexes; in general, men had a higher risk of antimicrobial resistance than women.
“These findings highlight important gaps in our knowledge of the epidemiology of antimicrobial resistance that are difficult to explain through known patterns of antibiotic exposure and healthcare contact,” the authors say.
“Our findings suggest that there may be value in considering interventions to reduce antimicrobial resistance burden that take into account important variations in antimicrobial resistance prevalence with age and sex.”
The authors add, “Our findings, that the prevalence of resistance in bloodstream infections across Europe varies substantially by age and sex, highlights important gaps in our knowledge of the spread and selection of AMR. In order for us to address this growing threat to public health, we now need data from a wider range of sources to determine the contribution that cultural versus natural history differences have in driving these patterns globally and the role that they play in the increasing rates of AMR being seen.”
Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. Study findings were published in the journal Immunity.
Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx.
EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers.
Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis.
There is no vaccine to prevent EBV infection nor a specific treatment.
In this study, investigators examined a viral protein called gp42, which the virus must use to infect B cells. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells.
The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42.
The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42.
Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.
Next, the scientists tested A10, 4C12 and several other mAbs in mice for their ability to prevent EBV infection and EBV lymphomas.
The mAb A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoproliferative disease or lymphoma.
In contrast, nearly all the mice treated with other mAbs became infected and some developed lymphoproliferative disease or lymphoma.
If future studies show mAb A10 to be safe and effective in humans, it could have clinical applications, particularly in people who have not been infected with EBV; those with immunodeficiency conditions, including severe combined immunodeficiency; or people receiving transplants.
People with such conditions are at risk of developing severe or fatal cases of EBV disease during their initial encounter with the virus.
The investigational monoclonal antibody could potentially be used prophylactically to prevent or better control EBV infections in such cases, the investigators note.
Additionally, the study team suggests that identification of the vulnerable sites on gp42 also paves the way to designing future vaccines that could elicit antibodies against one or both of the newly described sites.
An enthusiastic response to food in early childhood may be linked to a higher likelihood of experiencing eating disorder symptoms in adolescence, according to a new study led by researchers at UCL and Erasmus University Rotterdam.
The study, published in The Lancet Child & Adolescent Health, looked at survey data from 3670 young people in the UK and the Netherlands to investigate how appetite traits in early childhood might relate to the likelihood of developing eating disorder symptoms up to 10 years later.
The team also found that a slower pace of eating and feeling full more quickly (high sensitivity to satiety) in early childhood may be protective against developing some eating disorder symptoms later.
Co-lead author Dr Ivonne Derks (UCL Institute of Epidemiology & Health Care) said: “Although our study cannot prove causality, our findings suggest food cue responsiveness may be one predisposing risk factor for the onset of eating disorder symptoms in adolescence.
“However, high responsiveness to food is also a normal and very common behaviour and should be seen as just one potential risk factor among many rather than something to cause parents worry.”
Higher food responsiveness was linked to a 16% to 47% increase in the odds of reporting eating disorder symptoms, including binge eating symptoms, uncontrolled eating, emotional eating, restrained eating and compensatory behaviours.
The 47% increase was found for binge eating symptoms (eating a very large amount of food and/or experiencing the feeling of loss of control over eating), meaning that adolescents whose parents rated them highest on food responsiveness were almost three times more likely to report binge eating symptoms compared to adolescents whose parents scored them lowest.
A 16% increase in odds was found for restrained eating, whereby a person restricts their intake of food to lose weight or avoid weight gain.
Just like food responsiveness, emotional overeating in early childhood was also linked with higher odds of engaging in compensatory behaviours, which are intended to avoid weight gain, such as skipping meals, fasting and excessive exercise.
In turn, some appetite traits seemed to be protective against developing eating disorder symptoms later. Higher satiety responsiveness – that is, feeling full more quickly after eating, and feeling full for longer – was linked to lower odds of uncontrolled eating (defined as the extent to which someone feels out of control and eats more than usual) and compensatory behaviours.
A slower pace of eating, meanwhile, was linked to lower odds of compensatory behaviours and restrained eating.
The researchers also found that appetite traits such as food fussiness, emotional undereating (eating less due to low mood), and enjoyment of food in early childhood were not linked to later eating disorder symptoms in adolescence.
For the study, the researchers looked at data from two separate longitudinal studies: Generation R, following children born in Rotterdam, the Netherlands, between 2002 and 2006, and Gemini, which follows twins born in England and Wales in 2007.
Appetite traits were assessed based on parents’ questionnaire responses when the children were aged four or five. Eating disorder symptoms were self-reported by the then adolescents themselves at ages 12 to 14, when eating disorder symptoms typically start to emerge.
About 10% of the adolescents reported binge eating symptoms, where people eat an unusual amount of food and/or experience the feeling of loss of control over eating. Next to that, 50% reported at least one behaviour to compensate their food intake or to avoid gaining weight, such as skipping a meal.
Co-senior author Dr Clare Llewellyn (UCL Institute of Epidemiology & Health Care) said: “While the role of appetite in the development of obesity has been studied for many decades, this is the first study to comprehensively examine the role of appetite traits in the development of eating disorder symptoms.
“Eating disorders can be harder to treat effectively once they develop and so it would be better to prevent them from occurring in the first place. Our work in identifying risk factors in early life aims to support the development of possible prevention strategies. These could, for instance, involve providing extra support to children at higher risk.”
Appetite traits are divided into food approach appetitive traits (eg, food responsiveness, enjoyment of food, emotional overeating) and food avoidance traits (eg, satiety responsiveness, food fussiness, slowness in eating, emotional undereating).
The researchers found that non-responsive feeding practices, such as putting pressure on children to eat or using food as a reward or to soothe emotions, were linked to a higher likelihood of specific eating disorder symptoms later. However, the associations were small and varied between the two cohorts, and the researchers said further replication studies were needed.
Study reveals a significant link, suggesting that managing metabolic syndrome may help prevent cancer.
Source: Pixabay CC0
New research indicates that individuals with persistent and worsening metabolic syndrome – which encompasses conditions such as high blood pressure, elevated blood sugar, excess abdominal fat, and abnormal cholesterol – face an elevated risk of developing various types of cancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
In the study, 44 115 adults in China with an average age of 49 years were categorised into 4 different trajectories based on trends from 2006 (the time of the first physical exam) to 2010: 10.56% exhibited a low-stable pattern and maintained low metabolic syndrome scores; 40.84% exhibited a moderate-low pattern and maintained moderate to low metabolic syndrome scores; 41.46% exhibited a moderate-high pattern and consistently maintained moderate to high metabolic syndrome scores; and 7.14% exhibited an elevated-increasing pattern in which initially elevated metabolic syndrome scores increased over time.
During the follow-up period of 2010–2021, with a median follow-up of 9.4 years, there were 2271 cancer diagnoses among participants. Compared with participants with a low-stable trajectory pattern, those with an elevated-increasing trajectory pattern had 1.3-, 2.1-, 3.3-, 4.5-, 2.5-, and 1.6-times higher risks of developing any cancer, breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer, respectively.
Even when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined, the elevated-increasing trajectory pattern group had higher risks of developing all cancer types.
Also, participants with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of developing breast, endometrial, colon, and liver cancer, whereas the risk of kidney cancer was predominantly observed among participants with persistently high scores but without chronic inflammation.
“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” said senior author Han-Ping Shi, MD, PhD, of Capital Medical University, in Beijing. “Our study can guide future research into the biological mechanisms linking metabolic syndrome to cancer, potentially resulting in targeted treatments or preventive strategies. Formal evaluation of these interventions will be needed to determine if they are able to modulate cancer risk.”
A new study has tricked bacteria into sending death signals to stop the growth of biofilms that lead to deadly infections. The discovery by Washington State University researchers could someday be harnessed as an alternative to antibiotics for treating difficult infections.
Reporting in the journal,Biofilm, the researchers used the messengers, which they named death extracellular vesicles (D-EVs), to reduce growth of the bacterial communities by up to 99.99% in laboratory experiments.
“Adding the death extracellular vesicles to the bacterial environment, we are kind of cheating the bacteria cells,” said Mawra Gamal Saad, first author on the paper and a graduate student in WSU’s Gene and Linda Voiland School of Chemical Engineering and Bioengineering.
“The cells don’t know which type of EVs they are, but they take them up because they are used to taking them from their environment, and with that, the physiological signals inside the cells change from growth to death.”
Bacterial resistance is a growing problem around the world. In the US, at least 2 million infections and 23 000 deaths are attributable to antibiotic-resistant bacteria each year, according to the U.S. Centers for Disease Control.
When antibiotics are used to treat a bacterial infection, some of the bacteria can hide within their tough-to-penetrate biofilm. These subpopulations of resistor cells can survive treatment and are able to grow and multiply, resulting in chronic infections.
“They are resistant because they have a very advanced and well-organised adaptive system,” said Saad.
“Once there is a change in the environment, they can adapt their intracellular pathways very quickly and change it to resist the antibiotics.”
In their new study, the researchers discovered that the extracellular vesicles are key to managing the growth of the protective biofilm.
The vesicles, tiny bubbles from 30 to 50nm or about 2000 times smaller than a strand of hair, shuttle molecules from cells, entering and then re-programming neighbouring cells and acting as a cell-to-cell communications system.
As part of this study, the researchers extracted the vesicles from one type of bacteria that causes pneumonia and other serious infections.
They determined that the bacteria initially secrete vesicles, called growth EVs, with instructions to grow its biofilm, and then later, depending on available nutrients, oxygen availability and other factors, send EVs with new instructions to stop growing the biofilm.
The researchers were able to harness the vesicles with the instructions to stop growth and use them to fool the bacteria to kill off the biofilm at all stages of its growth.
Even when the biofilms were healthy and rapidly growing, they followed the new instructions from the death EVs and died. The death EVs can easily penetrate the biofilm because they are natural products secreted by the bacteria, and they have the same cell wall structure, so the cells don’t recognise them as a foreign enemy.
“By cheating the bacteria with these death EVs, we can control their behaviour without giving them the chance to develop resistance,” said Saad.
“The behavior of the biofilm just changed from growth to death.”
WSU Professor and corresponding author Wen-Ji Dong, who has been studying the vesicles for several years initially thought that all of the bacterial-secreted vesicles would promote cell growth.
The researchers were surprised when they found that older biofilms provided instructions on shutting themselves down.
“So now we’re paying attention to the extracellular vesicles secreted by older biofilms because they have therapeutic potential,” he said.
An innovative treatment significantly increases the survival of people with malignant mesothelioma, a rare but rapidly fatal type of cancer with few effective treatment options, according to results from a clinical trial led by Queen Mary University of London and published in JAMA Oncology.
The phase 3 clinical trial, led by Professor Peter Szlosarek at Queen Mary and sponsored by Polaris Pharmaceuticals, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), a rare and often rapidly fatal form of cancer with limited therapeutic options.
The ATOMIC-meso trial, a randomised placebo-controlled study of 249 patients with MPM, found that a treatment – which combines a new drug, ADI-PEG20, with traditional chemotherapy – increased the median survival of participants by 1.6 months, and quadrupled the survival at 36 months, compared to placebo-chemotherapy.
The findings are significant, as MPM has one of the lowest 5-year survival rates of any solid cancer of around 5-10%. This innovative approach marks the first successful combination of chemotherapy with a drug that targets cancer’s metabolism developed for this disease in 20 years.
MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with exposure to asbestos. It’s usually treated with potent chemotherapy drugs, but these are seldom able to halt the progression of the disease.
The premise behind this new drug treatment is elegant in its simplicity – starving the tumour by cutting off its food supply. All cells need nutrients to grow and multiply, including amino acids like arginine. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumour cells that can’t manufacture their arginine due to a missing enzyme, this means their growth is thwarted.
The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary’s Barts Cancer Institute that began with Professor Szlosarek’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. He and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM.
Professor Szlosarek said: “It’s truly wonderful to see the research into the arginine starvation of cancer cells come to fruition. This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma. I thank all the patients and families, investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy.”
There are ongoing studies assessing ADI-PEG20 in patients who have sarcoma or glioblastoma multiforme and other cancers dependent on arginine. The success of this novel chemotherapy in MPM also suggests that the drug may be of benefit in the treatment of multiple other types of cancer.
Spotlight visits Rahima Moosa Mother and Child Hospital and sees progress for the struggling hospital but also the reality that there’s a long road ahead to undo what a health ombud report suggests has been years of neglect and poor management.
Rahima Moosa Mother and Child Hospital serves up to 2 300 people admitted per month as well as 10 000 outpatients each month. (Photo: Denvor de Wee/Spotlight)
By Ufrieda Ho for Spotlight
It’s been a year since a damning Health Ombud’s report on the Rahima Moosa Mother and Child Hospital (RMMCH) was released. This month also marks the end of the last deadline the Gauteng Department of Health had to act on recommendations in the report.
At 80 years old, RMMCH is an iconic landmark on the western edge of Johannesburg. But it has gone from a one-time outlier for excellence to being in steady decline, marked by what the Ombud’s report criticised as incompetent leadership, neglect and crumbling infrastructure.
In May 2022, the hospital suffered a public low point when paediatric gastroenterologist, Dr Tim de Maayer, penned an open letter, slamming multiple failings at the facility. Public outcry from the letter, complaints from hospital users, and a widely circulated video of pregnant mothers sleeping on hospital corridor floors prompted the ombud’s investigation.
When Spotlight visited the hospital at the end of February (2024), there were positive outward signs that recent maintenance work had been completed, per the Ombud’s recommendations. Some areas have been painted and surfaces where underground sewer pipes had to be unblocked have also been tarred. The stench from overflowing sewage appears to be a thing of the past. Renovations to the antenatal care ward, shown in the video that went viral, are also near completion and the ward is expected to be operational again by the middle of March.
More signs that RMMCH is blipping on radars again include a new granite plaque at the entrance ready to be unveiled to commemorate the hospital in its 80th year. On noticeboards were flyers that advertised a community fun-walk for the end of February. It was an event intended to “reconnect” hospital staff with the immediate community it serves.
The hospital is also part of the roll-out of the provincial health information system (HIS) and admin staff were seen enrolling new patients on the system. The HIS is a long-awaited system to modernise patient file storage and make patient files accessible at facilities province-wide. Spotlight previously reported on the system.
These encouraging advances since the Ombud’s investigation get the thumbs up from hospital insiders. But they flag that even though the Gauteng Department of Health has announced a six-year renewal plan for the hospital and R53 million was approved in December 2023 for the next phase of renovations, the department is playing catch-up and still dragging its feet.
CT scan empty promises
For Dr Z, the biggest of her current concerns is that the hospital’s CT scan has not been in operation for the past 14 months. Dr Z asked not to be named because of the risk of victimisation.
“We have to beg other hospitals to do our scans. So even when you have a patient who actually needs a CT scan, you think twice – you ask yourself do they really, really need it or should you just watch them for another couple of months. It’s very demoralising and we keep hearing empty promises from management,” Dr Z says.
A shortage of clerical staff means clerks are shared between departments, resulting in inevitable administrative glitches and delays, Dr Z says.
There is also a growing need for child mental health services but the hospital doesn’t have in-patient psychiatry services and only has sessional psychological services.
“We serve an ever bigger community that has changing needs but our infrastructure has stayed the same and our staff numbers have not increased,” says Dr Z. The doctor has worked at RMMCH for nearly two decades – “my second home” she calls it.
The hospital has around 1200 staff members. They serve up to 2300 people admitted per month as well as 10 000 outpatients each month.
Dr Z tries to stay hopeful, saying “we look to the positive things and we do what we can”, but RMMCH can be a daunting place to work. Safety and security has resurfaced as a concern this February. This comes on the back of a car hijacking that took place in the hospital’s parking area at the beginning of the month. The Ombud’s report also looked into the hijacking of an intern’s car that took place in its investigation period.
Parking too is a daily frustration – there are only 300 parking spots for staff on the hospital campus but at least 400 vehicles that need a place to park at peak times. Visitors are told to park on the streets.
‘Mr Fixer’
Acting CEO of the hospital Dr Arthur Manning met with Spotlight to answer questions put to him and to the Gauteng Department of Health.
Manning took up the job in September 2022 as part of the Ombud’s recommendation to redeploy the previous CEO, Dr Nozuko Mkabayi, whom the government oversight body found to be a dismal failure.
Manning calls himself “a fixer”. His role, he recognises, has been to help stop the slide for RMMCH, also to boost staff morale, restore communication channels and regain the community’s trust in the facility.
“We are a system under pressure and we know there is burnout and low morale but we have improved counselling support and we try to recognise and thank people. We held a nurse’s awards dinner last year exactly for these reasons,” he says.
Manning says the hospital organogram was last updated in 2006, but he has submitted a revised one to the Gauteng Department of Health. It makes the case for more admin and support staff, more junior and training doctor posts and bolstering psychiatric and psychological services. These, he says, are especially necessary because services for children are particularly neglected.
The broken CT scanner at Rahima Moosa Mother and Child Hospital. (Photo: Denvor de Wee/Spotlight)
On the matter of the CT scanner, he says “procurement is underway”. It’s a planning failure that the machine is five years beyond its expected lifespan and was not replaced sooner, resulting in the current gap. Manning says the Gauteng Department of Health is now piggybacking on Limpopo’s procurement contract. Piggybacking refers to provisions in the Public Finance Management Act, that under certain conditions, allow a department in one province to procure goods and services via a contract that a department in another province has concluded with a service provider.
According to Manning, the Gauteng province is currently concluding an X-ray equipment tender that has delayed the procurement of the CT scanner for RMMCH. “Without a tender in place, procurement is more difficult,” he says. Approval to use Limpopo’s tender contract cuts out some red tape and means the CT scanner and maintenance contract has been secured at the price of R30 million. By May, he says, the hospital will also have an MRI-scanning facility.
Staff helps to spruce up waiting area
Manning has been credited by some for shifting morale and competently overseeing the interventions set out by the Ombud’s report. On a hospital walkthrough with Spotlight, he engages casually with staff and patients. He’s also evidently proud of staff-driven initiatives to improve the hospital experience for patients. He points out a freshly painted waiting area in one of the departments where children are playing with new toys and crawling on bright green astro turf. More than half the money for this project came from doctors and nurses raising funds cycling and running in race events in the city.
Keeping staff motivated means their concerns and working conditions – including the parking problem and safety and security – have to be priorities, he says.
Cars are double and triple-parked in the overcrowded staff parking area. Currently, informal management of this is done via Whatsapp groups. People on the groups are notified to move their cars as spots free up. Manning says the hospital is working to secure nearby grounds for additional parking. On safety and security, he says the hospital has stepped up collaboration with local police and the community policing forums to increase patrolling around the hospital especially around shift changes. He adds: “We have expanded our CCTV camera coverage, requested for armed security control and we’re exploring panic button systems.”
A bigger budget and a permanent CEO
There are two key outstanding issues from the Ombud’s report. The first is reclassification of the hospital that is also an academic and training hospital, from a regional facility to a tertiary hospital.
“This is something that involves national, but when reclassification is done it will means RMMCH’s budgets and grants will be adjusted and we will be able to do so much more,” says Manning.
The second issue is the appointment of a permanent CEO, which Manning says is “being handled by central office”. He side-steps a question on whether his name is in the mix. It’s expected that an announcement on the new CEO will take place in April.
Professor Ashraf Coovadia is academic head of Paediatrics and Child Health at Wits University and heads up this department at RMMCH. He says Manning has “been good for RMMCH” but he says above the level of CEO, it’s the Gauteng Department of Health that needs to get its house in order . He says there has been a lack of communication, consultation, transparency and decisive action from the Gauteng Department of Health for years.
“A CEO can do only so much. When we have having acting heads in so many departments who are in acting positions for forever, it’s a joke. It means decisions don’t get made or decisions don’t get made for the long run and this compromises how the hospital is run and the care we give patients,” he says.
He adds that when there is less “hospital floor” consultation and more bureaucratic centralisation from the department it alienates doctors and nurses. “It becomes more and more difficult to try to motivate especially junior doctors who start off wanting to give back to the public health service but become so frustrated they don’t stay.”
Back to the 1900s
Like Dr Z, Coovadia highlights the CT scan issue, as well as the long delays and the excuses for the delays.
“Working without a scanner takes us back to the 1900s; we are not practising modern medicine and we are not able to diagnose patients early enough,” he says.
Coovadia adds that even though water and electricity supply issues at RMMCH have improved, infrastructure fixes remain patchy. “There are fewer issues of burst pipes and flooding, but it’s still happening.”
Coovadia has been with the hospital for 26 years, he knows better than most the precariousness of the situation and why the hospital is not yet out of the woods. He says: “The negative attention on the hospital did bring about some positive change. But it can make you cry when you see the slide over the last ten years… The hospital is not collapsing, but there are daily collapses.”
NOTE: Coovadia is on the board of SECTION27. Spotlight is published by SECTION27, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Investing in women’s health is not only a moral imperative; it makes economic sense. International Women’s Day (8 March 2024) should serve as a rallying cry that it is time to turn talk into action – and a lasting commitment to regenerating women’s health.
“Shaping the private and public health agenda through increased advocacy and awareness, with governments and medical professionals putting women’s health on – and higher up – the agenda and targeting sources of stigma and bias – this is what we need to do right now,” says Jo Pohl, Associate Director at global management consultancy Kearney.
Pohl was speaking (this week) on the eve of International Women’s Day, and following an event organised by Kearney to commemorate the day. Guests listened to the story of ‘Tina B’, the longest-surviving heart and bilateral lung transplant recipient in Africa (during a gathering at Kearney’s Johannesburg offices on Wednesday 6 March 2024).
The event explored Tina’s resilience, the challenges she faced, the odds she beat, and just how different her journey could have been with the advent of Artificial Intelligence (AI) in donor healthcare decision-making.
She shared her opinion on the use of AI in selecting organ donors. Tina told guests at the event that she believes if AI had to decide whether she should receive her surgery or not, it would have decided against her based on inherent biases or rather what the AI was asked to solve for.
According to her, AI would have assessed the state of her lungs and heart and potentially rejected her as a candidate for organ donation. Since she needed three organs, AI would have viewed her as one, high risk candidate versus the potential to save three “better” candidates.
The human element – from intuition to hope and optimism – is key. She told guests that her doctors echoed the same in terms of leveraging experience, expertise, and an understanding of a patient’s mindset.
“I am not an expert in AI, but I am an expert in being a patient,” she said. “AI could help inform options but needs to be questioned, and experienced doctors need to be able to apply their human intuition in any results.”
Typically, there are over 4000 people on the organ transplant waiting list at any given time, with only 0.2% of the population opting-in for organ donation. These kinds of numbers lead to questions such as “how is one candidate chosen over another and why”, questions that become even more important as we increasingly incorporate AI in healthcare decisions.
“Just think of the implications for healthcare professionals, researchers, and policymakers to develop and implement AI in healthcare ethically, equitably, and inclusively, if we consider transplant patients,” says Pohl.
“AI in healthcare should be used to benefit all members of society, regardless of gender, race, or socio-economic status. How can we co-create a world where everyone is seen, heard and the human considered in healthcare decision-making,” says Theo Sibiya, Kearney’s Africa MD.
“There needs to be a deliberate focus on keeping women front of mind and lending our expertise to continue breaking down barriers such as the gender health gap by redesigning healthcare that can put women first,” he adds.
Tina B has now become an advocate for organ donation and aims to help others going through the waiting process. She told guests of her experience of having to wait three years on the organ donor waiting list.
“You start to lose hope. You get excited to get on the list, but time drags on, and your body starts to fail you…it is a very dark place. I was tired of fighting to breathe, to stay awake; I remember saying to my God if you don’t give me a transplant, then take me home.”
AI has the potential to revolutionise the healthcare industry. With the ability to analyse large amounts of data quickly, AI can help healthcare professionals make more informed decisions, improving patient outcomes. It is an “and” versus “or” proposition.
“We need to be mindful, however, of inherent gender biases, overcome programming that favours males, and address flaws in the interpretation of data that exclude human perspectives. Doing so can make AI in healthcare more representative and inclusive,” says Sibiya.
Pohl explains that a women-informed lens is essential to ensuring equity and inclusivity in AI development and application.
“Regenerate is Kearney’s answer to “what’s next” in a post-resilience world and a timely approach to how businesses can and should be ready for the future. Tina B is a living example of regeneration, her story amplifies our Kearney commitment to a global campaign to “be the difference” for women’s health which we launched in Davos earlier this year,” says Sibiya.
“This amplifies our vision, rooted in a regenerative mindset that recognises the interconnectedness of our actions and their impact on the world around us, including how we make and execute healthcare and people decisions.”
As part of this vision, an open letter was released by Kearney and FemTechnology during the World Economic Forum Annual Meeting on behalf of the Redesigning Healthcare with Women in Mind signatories.
The letter is addressed to all those within the healthcare ecosystem whose innovations have impact and decisions have power: from pharma, biotech, and medtech firms to investors, tech companies, and consumer health players serving women and girls.
The signatories call for a commitment to challenge institutional gender inequalities and shape the future of public and private healthcare for those it has failed for far too long.
