Scanning Electron Micrograph of Pseudomonas aeruginosa. Credit: CDC/Janice Carr
Pseudomonas aeruginosa bacteria are a common menace in hospital wards, causing life-threatening infections, and are often resistant to antibiotics. Researchers have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections, which could also be a target for future treatments. The results were recently appeared in the journal EMBO Reports.
Many bacterial species use sugar-binding molecules called lectins to attach to and invade host cells. Lectins can also influence the immune response to bacterial infections. However, these functions have hardly been researched so far. A research consortium led by Prof Dr Winfried Römer at the University of Freiburg and Prof Dr Christopher G. Mueller at the CNRS/University of Strasbourg has investigated the effect of the lectin LecB from P. aeruginosa on the immune system. It found that isolated LecB can render immune cells ineffective: The cells are then no longer able to migrate through the body and trigger an immune response. The administration of a substance directed against LecB prevented this effect and led to the immune cells being able to move unhindered again.
LecB blockades immune cells
As soon as they perceive an infection, cells of the innate immune system migrate to a nearby lymph node, where they activate T and B cells, triggering a targeted immune response. LecB, according to the current study, prevents this migration. “We assume that LecB not only acts on the immune cells themselves in this process, but also has an unexpected effect on the cells lining the inside of the blood and lymph vessels,” Römer explains. “When LecB binds to these cells, it triggers extensive changes in them.” Indeed, the researchers observed that important structural molecules were relocated to the interior of the cells and degraded. At the same time, the cell skeleton became more rigid. “The cell layer thus becomes an impenetrable barrier for the immune cells,” Römer said.
An effective agent against LecB
Can this effect be prevented? To find out, the researchers tested a specific LecB inhibitor that resembles the sugar building blocks to which LecB otherwise binds. “The inhibitor prevented the changes in the cells, and T-cell activation was possible again,” Mueller said. The inhibitor was developed by Prof Dr Alexander Titz, who conducts research at the Helmholtz Institute for Pharmaceutical Research Saarland and Saarland University.
Further studies are needed to determine how clinically relevant the inhibition of the immune system by LecB is to the spread of P. aeruginosa infection and whether the LecB inhibitor has potential for therapeutic application. “The current results provide further evidence that lectins are a useful target for the development of new therapies, especially for antibiotic-resistant pathogens such as P. aeruginosa,” the authors conclude.
Canadian and UK researchers explored the relationship between vitamin D supplementation and dementia in more than 12 388 participants of the US National Alzheimer’s Coordinating Center, who had a mean age of 71 and were dementia-free when they signed up.
The team found that taking vitamin D was associated with living dementia-free for longer, and they also found 40% fewer dementia diagnoses in the group who took supplements.
Of the group, 2696 participants progressed to dementia over ten years; amongst them, 2017 (75%) had no exposure to vitamin D throughout all visits prior to dementia diagnosis, and 679 (25%) had baseline exposure.
Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”
While Vitamin D was effective in all groups, the team found that effects were significantly greater in females, compared to males. Similarly, effects were greater in people with normal cognition, compared to those who reported signs of mild cognitive impairment – changes to cognition which have been linked to a higher risk of dementia.
The effects of vitamin D were also significantly greater in people who did not carry the APOEe4 gene, known to present a higher risk for Alzheimer’s dementia, compared to non-carriers. The authors suggest that people who carry the APOEe4 gene absorb vitamin D better from their intestine, which might reduce the vitamin D supplementation effect. However, no blood levels were drawn to test this hypothesis.
Previous research has found that low levels of vitamin D are linked to higher dementia risk. Vitamin D is involved in the clearance of amyloid in the brain, the accumulation of which is one of the hallmarks of Alzheimer’s disease. Studies have also found that vitamin D may provide help to protect the brain against build-up of tau, another protein involved in the development of dementia.
Co-author Dr Byron Creese, at the University of Exeter, said: “Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected. The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case. The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time.”
People undergoing hormone replacement therapy (HRT) for gender dysphoria have a greatly increased risk of serious cardiac events, according to a study presented at the American College of Cardiology annual meeting. Compared to people with gender dysphoria not taking HRT, those taking HRTY saw a seven-fold risk increase for ischaemic stroke, and risk increases for myocardial infarction and pulmonary embolism.
People with gender dysphoria may use HRT as part of gender affirmation therapy to transition to a different gender than their biological sex at birth. HRT for this purpose is rapidly increasing, especially among teens and young adults.
Previous research on hormone-modulating medications has primarily focused on younger women using hormone-based birth control or on older women following a hysterectomy or during menopause. In these populations, long-term HRT has been associated with an increased risk of breast cancer, stroke and blood clots.
Researchers retrospectively examined rates of cardiovascular events in over 21 000 people with gender dysphoria from a national database of hospital records, of whom 1675 had used HRT. Typically, people assigned male at birth receive oestrogen and people assigned female at birth receive testosterone. Overall results found hormone replacements were associated with higher rates of cardiac events, mostly related to dangerous blood clots, but were not associated with higher rates of death.
Compared with hospitalised patients with gender dysphoria who had never used HRT, those taking gender affirmation HRT had higher rates for a range of in-hospital cardiovascular events:
ST-elevation myocardial infarction (OR 5.90, 95% CI 1.07-32.42)
Ischaemic cerebrovascular accident (OR 7.15, 95% CI 2.74-18.67)
Non-ST-elevation myocardial infarction (OR 3.30, 95% CI 1.20-9.04)
Pulmonary embolism (OR 4.92, 95% CI 2.08-11.62)
“It’s all about risks and benefits. Starting transitioning is a big part of a person’s life and helping them feel more themselves, but hormone replacement therapy also has a lot of side effects – it’s not a risk-free endeavour,” said Ibrahim Ahmed, MD, a third-year resident at Mercy Catholic Medical Center in Darby, Pennsylvania and the study’s lead author.
HRT was not associated with any increase in deaths, incident atrial fibrillation, diabetes, hypertension, haemorrhagic stroke, or heart failure.
Both oestrogen and testosterone are known to increase the clotting activity of blood, which could explain the increase in clotting-related cardiovascular events, researchers said. Those taking hormone replacement therapy also had higher rates of substance use disorder and hypothyroidism.
“Looking at a person’s medical and family history should definitely be part of the screening protocol before they even start hormone replacement therapy,” Ahmed said. “It is also important that people considering this therapy are made aware of all the risks.”
One limitation of the study is that it only accounted for whether individuals had ever used any type of hormone replacement therapy. To better inform clinical decisions, researchers said it would be helpful to assess whether the duration of treatment, the age at which it is initiated or the type of hormone therapy used affects the risks.
“I’m curious to see if the method of administration alters the outcomes,” Ahmed said. “Is one way of giving hormone replacement therapy better or associated with a lower risk of cardiovascular outcomes? If so, then that should be the focus for how we give these patients their hormone replacement therapy going forward.”
In addition to considering ways to mitigate potential cardiovascular risks before starting hormone replacement therapy for individual patients, researchers said it will be important to continue to study potential long-term cardiovascular and other health effects of gender affirmation therapies as the use of these therapies become more common.
An international Task Force has recommended a method to help diagnose preschool age children with Primary Ciliary Dyskinesia (PCD), a rare, inherited condition that leads to chronic lung, ear and sinus infections. The Task Force’s findings were published in the European Respiratory Journal.
Children with PCD have a problem with mucus build-up, which leads to inflammation in the airways and infections in the lungs, nose, sinuses and ears. Most people with PCD have symptoms from birth or early childhood. But some children with PCD may not be diagnosed until much later.
Currently, a commonly used diagnostic test for PCD is measuring the nitric oxide (nNO) in the nose using a chemiluminescent analyser. This involves holding a sampling tube at the nostril, whilst the patient either holds their breath, or breathes out through their mouth against a resistance – but for young children such controlled breathing isn’t always practical. Furthermore, chemiluminescence analysers are extremely expensive, not portable, and not available in most countries.
Jane Lucas, Professor of Paediatric Respiratory Medicine at University of South Hampton, led an international Task Force to review existing studies and literature to establish whether there were more effective and accessible methods of diagnosis for PCD in younger children.
The task force concluded that although holding the breath or breathing against a resistor whilst using a chemiluminescence analyser was more reliable in older children and adults, adequate measurements could be achieved by measuring nasal nitric oxide whilst a pre-school child breathes normally and should be the standard way when diagnosing PCD in children under the age of five.
The Task Force also suggested that although chemiluminescence analysers are more reliable, the relatively inexpensive electrochemical devices have a role in healthcare systems with limited resources. They also recognised that the portability of electrochemical devices may be useful in countries where patients live long distances from a specialist centre, enabling the specialist to travel to the patient.
“We know that the earlier we can diagnose a condition, the better the chances are of implementing the best treatment plan for the patient,” Professor Lucas said. “But current guidelines and technical standards focus on nNO measurements in older, cooperative children using technology that is not widely available.
“Pre-schoolers often need different methods to be employed when measuring nNO, methods that are less invasive and adaptable. Without guidelines for younger children, and electrochemical analysers there is huge variability in how people take the measurements and interpret them.
“This paper is the first step towards standardising sampling, analysis, and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups including preschool-age children. We hope this will promote earlier diagnosis of PCD, and a standardised approach to interpreting and reporting results.”
The task force also recommends that future research is needed to ensure the technical standard is kept up to date.
According to a new study published in Acta Obstetricia et Gynecologica Scandinavica, in women with uncomplicated pregnancies, elective induction of labour at any point between 37 and 41 weeks was consistently associated with those children having lower scholasti performance at age 12.
Investigators analysed data for 266 684 children born between 37 and 42 weeks from uncomplicated pregnancies in white women in the Netherlands. Scholastic performance scores at age 12 years were lower in those from pregnancies with induced labour at 37–41 weeks compared with those with uninduced labour. At 42 weeks, there was no significant difference in scholastic performance between these groups.
The proportion of children who reached higher secondary school level was significantly lower after induction of labour at each gestational week from 38–41 weeks. For example, at 38 weeks, rates were 48% versus 54% in induced versus uninduced. (In the Dutch education system, when children reach the end of primary school, around 12 years of age, they are divided over four different levels of secondary education according to their intellectual ability. All children in the last year of regular primary education take a test to guide the choice of level of secondary education.)
“Of course, if there is an indication to induce delivery before 41 weeks, there is little doubt we should do this. But if the reason is purely elective, it is reasonable to be cautious of these subtle adverse effects,” said Wessel Ganzevoort, MD, PhD, senior investigator and maternal foetal medicine specialist at Amsterdam UMC.
By Yanga Nokhepheyi, Marlise Richter, and Fatima Hassan for Spotlight
A frightful piece of information came to light recently. The pharmaceutical giant Pfizer announced its 2022 revenue at $100 billion. This is more than the combined health spending of 108 countries in 2020 according to calculations of The People’s Vaccine Campaign. The Pfizer COVID vaccine, of course, helped the dollars roll in. In fact, some reports suggest that Pfizer charged some countries $130 per dose of vaccine, while it is estimated that it costs less than $2 per dose to make. That equated to a markup of a stupefying 10 000% but we don’t know the full pricing details because the contracts are marked ‘secret’.
Figures like these make one’s eyes water.
In this pandemic, tackling the pharmaceutical sector and the perversities of its pandemic profiteering has been the focus of an international movement of health activists united under the banner of the People Vaccine Campaign. Partly because of severe resistance by governments in the global north and inaction locally, access to timely supplies of affordable and essential COVID vaccines, medicines and diagnostics has not materialised. But the struggle continues not only to tackle these structural barriers to beat COVID and future pandemics but also to help ensure implementation of Universal Health Coverage (UHC) systems. UHC means that everyone would be able to get the quality health services they need and benefit from scientific progress – irrespective of their ability to pay and without having to face financial hardship.
A Herculean task
South Africa, too, has committed to attaining UHC by 2030 as part of a set of promises made on the United Nation’s Sustainable Development Goals. South Africa’s main strategy to attain UHC is to implement a National Health Insurance (NHI) system. Unfortunately, progress has been historically slow, but in the build-up to the 2024 elections, the African National Congress (ANC) Members of Parliament (MPs) are rushing the law reform process despite an acknowledgement even from the health ministry that progress and timelines are hampered by the socio and mainly economic impacts of the pandemic. This includes a fiscus crisis with additional pandemic-related debt, and according to Dr Nicholas Crisp, Deputy Director-General in the health department responsible for NHI, “the NHI could take decades to be implemented at full scale”.
It will require a Herculean task to unify our apartheid-era two-tiered healthcare system, with the right skills, funding base, and transparency in decision-making around health policy and medicine selection. The pandemic has highlighted why all these elements are critical for healthcare for everyone.
We provide a short overview of our research below.
Law reform
Last year, the Portfolio Committee on Health in Parliament deliberated on the ‘NHI Bill’, but there were no significant changes made to it. It needs major revision. Many serious concerns and recommendations from parliamentary submissions by multiple stakeholders have gone unaddressed. The Health Justice Initiative (HJI) has focused on medicine procurement provisions in the Bill and in 2022 raised at least 17 questions that require greater attention before the law is passed. Neglecting to address the public’s submissions is not surprising seeing that ANC MPs serving on the committee were resolute in having the National Assembly adopt the Bill before the ANC Conference in December 2022. However, time ran out before the adoption of the Bill by Parliament, and the Parliamentary process is seemingly going to resume this month.
Stakeholder submissions to Parliament on the Bill (of which there were 64 000 written submissions following Parliament’s call for comment in 2019) and various commentators have warned about the ‘looming disaster’ that the Bill in its current form poses, but they are often divided on the main reasons. A tiny minority resists the principle of unified health systems and Universal Health Care for all (meaning, also for the poor). Many more groups agree that NHI is an ethical necessity but are concerned about South Africa’s disintegrating public health system, energy crisis, high levels of state corruption involving health product procurement, and the in/ability of the Department of Health to actually implement NHI in its current proposed form.
Other groups have rightfully pointed out concerns over conferring too much power on the Minister of Health, inadequate financing models, the feasibility of NHI in SA post-COVID, and the exclusion of specific categories of people from NHI. (For a curated archive of critical submissions, please see here).
Risks to medicine access
Regrettably, the provisions in the Bill on Medicine Selection, Pricing, and Procurement are ambiguous at best, and as the HJI pointed out in 2022, the entire shift of our medicine selection, procurement, and reimbursement system to “NHI reimbursement” has not been adequately thought through, potentially posing a great risk for the future of medicine selection and access in the country for all people. This requires immediate attention at the highest levels of the executive and the legislature too – and likely needs a multi-department and stakeholder technical group to urgently determine the exact trajectory of this planned process.
The World Health Organization has emphasised that UHC programmes will only be successful if there is “affordable access to safe, effective, and quality medicines and health products”. In addition, the COVID pandemic has taught us that timely and fairly priced access to essential diagnostics, therapeutics, and vaccines is key to addressing any public health emergency and improving health outcomes. We cannot safeguard public health without access to medicines – procured fairly, delivered on time, and based on expert and transparent decision-making and approval.
The cost of medicine, as elsewhere in the world where there are national health systems, remains a key concern. The Minister of Health last November in the National Assembly said that the funds for the NHI would be collected through a combination of taxes, including the reallocation of medical scheme credits paid to medical schemes, provincial health budgets to the NHI Funds, and payroll tax.
The financial feasibility of implementing the NHI is still unclear and a huge risk to the fiscus in a post-COVID economy that is dealing with a recession, load shedding, and high unemployment rates.
In late 2022, HJI argued that the Bill does not adequately consider the complexities of medicines access and that our medicines system could be severely jeopardised if poorly drafted sections in the current Bill become law. We said that government should set up a task team to urgently determine the exact trajectory of this planned process.
The Health Department’s recent response to submissions and its own recommendations on amendments to the Bill sadly does not realise the gravity of the threat to the future of medicine selection and access.
17 questions
In HJI’s 2022 analysis of the Bill, we raised 17 key questions that we believe must be addressed by lawmakers in the next version of the Bill and before NHI comes into effect. These include:
What specific measures are envisaged to enable and promote public transparency related to medicine selection, procurement, and contracting processes under the NHI?
How will the price of medicines not included in or covered by the NHI be regulated? And what role will External Reference Pricing (ERP) methodology play in the NHI and beyond?
How will the NHI Fund (e.g., the Office of Health Products Procurement, the NHI Board) negotiate with global pharmaceutical manufacturers and suppliers to procure for government and how will that process be transparent and accountable?
How will the Minister determine that the NHI is ‘fully implemented’, and what will take place in terms of what medical schemes can and cannot offer members during the transition period, and after the (undefined) date?
Has consideration been given to designing a competitive and different single medicine pricing system for SA?
Drawing on our work on medicine access during the HIV and COVID pandemic, we appreciate that there are powerful vested interests located in the multi-trillion-dollar pharmaceutical industry – this is why there is a need for legal safeguards, sound legislation, and independent and transparent institutions to ensure access to affordable medicines for all of us living here.
The pandemic showed that a lack of transparency, autonomy, and information around expert advice can bedevil open government decision-making. Secret procurement contracts for essential vaccines could become the norm even under NHI as they did in COVID, something we are fighting in our courts to open up, later this year.
Figuring out a sound system for a unified medicine access system under NHI is a formidable undertaking that requires a multi-disciplinary task team with experts from various fields, experience, and technical know-how. It is not easy to simply merge two parallel medicine procurement and selection systems. The risk is that the status quo could continue – where the rich and insured access the best medicines at a higher price.
We believe that the principles underpinning NHI for our highly regressive, unequal two-tiered healthcare system are too important for our collective health, well-being, and our Constitutional democracy to have lacklustre legal provisions and worrying gaps on the essential issues of medicine procurement and selection.
As the Bill currently stands, it will strengthen the private healthcare sector’s stranglehold on us and our fiscus. It will leave us at the mercy of advisory committees that bear no duty to be transparent in deciding which medicines you and I will be able to access under NHI.
We can and need to do better.
* Nokhepheyi and Richter are researchers and Hassan the Director of the Health Justice Initiative.
A device that uses ultrasound to calm overactive nerves in the kidneys may be able to help some people get their blood pressure under control, according to successful test results published in JAMA Cardiology.
Led by researchers at Columbia University and Université de Paris, the study has found that the device consistently reduced daytime ambulatory blood pressure by an average of 8.5 points among middle-aged people with hypertension.
Lifestyle changes, such as cutting salt intake or losing weight, along with medications are often prescribed to lower blood pressure in patients with hypertension. Yet about one-third of hypertensive patients have resistant hypertension.
“Many patients in our clinical practice are just like the patients in our study, with uncontrolled blood pressure in the 150s despite some efforts,” says Ajay Kirtane, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and co-leader of the study.
Leaving blood pressure uncontrolled for too long can lead to heart failure, strokes, heart attacks, and irreversible kidney damage.
“Renal ultrasound could be offered to patients who are unable to get their blood pressure under control after trying lifestyle changes and drug therapy, before these events occur,” says Kirtane, who is also an interventional cardiologist and director of cardiac catheterisation laboratories at NewYork-Presbyterian/Columbia University Irving Medical Center.
The study tested the device, which is used in an outpatient procedure called ultrasound renal denervation. The device is still investigational and has not yet been approved by the FDA for use outside of clinical trials.
Kidney nerves and hypertension
Hypertension in middle age is thought to be caused in part by overactive nerves in the kidneys, which trigger water and sodium retention and release hormones that can raise blood pressure. (In older people, hypertension often occurs as blood vessels stiffen). Antihypertensive drugs work in different ways to lower blood pressure, by dilating blood vessels, removing excess fluid, or blocking hormones that raise blood pressure. But none target the renal nerves directly.
Ultrasound therapy calms overactive nerves in the renal artery, disrupting signals that lead to hypertension. The therapy is delivered to the nerves via a thin catheter that is inserted into a vein in the leg or wrist and threaded to the kidney.
Study results
The new study pooled data from three randomised trials encompassing more than 500 middle-aged patients with varying degrees of hypertension and medication use.
Twice as many patients who received the ultrasound therapy reached their target daytime blood pressure (less than 135/85 mmHg) compared to patients in the sham groups.
“The result was almost identical across the different study groups, which definitively shows that the device can lower blood pressure in a broad range of patients,” Kirtane says.
The procedure was well-tolerated, and most patients were discharged from the hospital the same day. According to Kirtane, improvements in blood pressure were seen as soon as one month after the procedure.
The treatment will be evaluated by the FDA in the coming months.
Bottom line for patients with resistant hypertension
The investigators expect the treatment could be offered as an adjunct to medication therapy and lifestyle changes for patients with uncontrolled hypertension.
“Once the device is available, we envision recommending it to patients who have tried other therapies first. The hope is that by controlling blood pressure, we might be able to prevent kidney damage and other effects of uncontrolled blood pressure,” Kirtane adds.
A “biocomputer” powered by human brain cells could be developed within our lifetime, according to an article in the journal Frontiers in Science. The Johns Hopkins University researchers expect such “organoid intelligence” technology to exponentially expand the capabilities of modern computing and create novel fields of study, as well as yielding insights into neurodegenerative diseases.
“Computing and artificial intelligence have been driving the technology revolution but they are reaching a ceiling,” said Thomas Hartung, a professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health and Whiting School of Engineering who is spearheading the work. “Biocomputing is an enormous effort of compacting computational power and increasing its efficiency to push past our current technological limits.”
For nearly two decades scientists have used tiny organoids, lab-grown tissue resembling fully grown organs, to experiment on kidneys, lungs, and other organs without resorting to human or animal testing. More recently Hartung and colleagues at Johns Hopkins have been working with brain organoids, orbs the size of a pen dot with neurons and other features that promise to sustain basic functions like learning and remembering.
“This opens up research on how the human brain works,” Hartung said. “Because you can start manipulating the system, doing things you cannot ethically do with human brains.”
Hartung began to grow and assemble brain cells into functional organoids in 2012 using cells from human skin samples reprogrammed into an embryonic stem cell-like state. Each organoid contains about 50 000 cells, about the size of a fruit fly’s nervous system. He now envisions building a futuristic computer with such brain organoids.
Computers that run on this “biological hardware” could in the next decade begin to alleviate energy-consumption demands of supercomputing that are becoming increasingly unsustainable, Hartung said. Even though computers process calculations involving numbers and data faster than humans, brains are much smarter in making complex logical decisions, like telling a dog from a cat.
“The brain is still unmatched by modern computers,” Hartung said. “Frontier, the latest supercomputer in Kentucky, is a $600 million, 6,800-square-feet installation. Only in June of last year, it exceeded for the first time the computational capacity of a single human brain – but using a million times more energy.”
It might take decades before organoid intelligence can power a system as smart as a mouse, Hartung said. But by scaling up production of brain organoids and training them with artificial intelligence, he foresees a future where biocomputers support superior computing speed, processing power, data efficiency, and storage capabilities.
“It will take decades before we achieve the goal of something comparable to any type of computer,” Hartung said. “But if we don’t start creating funding programs for this, it will be much more difficult.”
Medical applications
Organoid intelligence could also revolutionise drug testing research for neurodevelopmental disorders and neurodegeneration, said Lena Smirnova, a Johns Hopkins assistant professor of environmental health and engineering who co-leads the investigations.
“We want to compare brain organoids from typically developed donors versus brain organoids from donors with autism,” Smirnova said. “The tools we are developing towards biological computing are the same tools that will allow us to understand changes in neuronal networks specific for autism, without having to use animals or to access patients, so we can understand the underlying mechanisms of why patients have these cognition issues and impairments.”
To assess the ethical implications of working with organoid intelligence, a diverse consortium of scientists, bioethicists, and members of the public have been embedded within the team.
Eliminating animal milk alone from the diet of adults with eosinophilic oesophagitis (EoE) is as effective at treating the disease as eliminating animal milk plus five other common foods, according to a clinical trial published in The Lancet Gastroenterology & Hepatology. For people with EoE whose disease remains active after they cut out animal milk, a more restrictive diet may help them achieve remission, according to the researchers.
“Diet-based therapy for eosinophilic esophagitis will be much easier to follow for many people if it involves cutting just one food from the diet rather than six,” said Hugh Auchincloss, M.D., acting director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.
EoE is a chronic disease characterised by an overabundance of white blood cells called eosinophils in the pesophagus. Food allergy inflammation drives the disease by damaging the oesophagus and preventing it from working properly. For people with EoE, swallowing even small amounts of food can be a painful and stressful choking experience.
Excluding certain foods from the diet has been a cornerstone of EoE treatment. During the early 2000s, researchers found that eliminating six common food triggers of oesophageal injury (milk, egg, wheat, soy, fish and nuts) substantially reduced signs and symptoms of EoE. This six-food elimination diet (6FED) became a common approach to managing the disease.
In recent years, scientists have conducted small, non-randomised studies of removing one to four of the most common food antigens from the diet to treat EoE, with some success. However, the relative risks and benefits of eliminating many foods versus a few foods at the start of diet-based therapy remained unclear.
The multi-site, randomised trial involved 129 adults ages 18 to 60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in oesophageal tissue. Participants were randomised to either the 1FED, which eliminated only animal milk from the diet, or the 6FED. They followed their assigned diet for six weeks, then underwent an upper endoscopy exam and an oesophageal tissue biopsy. If the number of eosinophils in the tissue indicated that EoE was in remission, the participant exited the study. If EoE was not in remission, people who had been on 1FED could advance to 6FED, and people who had been on 6FED could take topical swallowed steroids, both for six weeks, followed by a repeat exam with tissue biopsy.
The investigators found that 34% of participants on 6FED and 40% of participants on 1FED achieved remission after six weeks of diet therapy, a difference that was not statistically significant. The two diets also had a similar impact across several other measures, including reduction in EoE symptoms and effect on quality of life. Thus, 1FED and 6FED were equally effective at treating EoE, an unexpected finding.
The researchers also discovered that nearly half of people who did not respond to 1FED attained remission after treatment with the more restrictive 6FED, while more than 80% of the non-responders to 6FED achieved remission with oral steroids.
Taken together, the investigators conclude that 1FED is a reasonable first-line diet therapy option in adults with EoE, and that effective therapies are available for people who do not achieve remission after 1FED or 6FED.
One in ten early deaths could be prevented if everyone managed at least half the recommended level of physical activity, say a team led by researchers at the University of Cambridge.
In a study published today in the British Journal of Sports Medicine, the researchers say that 11 minutes a day (75 minutes a week) of moderate-intensity physical activity – such as a brisk walk – would be sufficient to lower the risk of diseases such as heart disease, stroke and a number of cancers.
Cardiovascular diseases – such as heart disease and stroke – are the leading cause of death globally, responsible for 17.9 million deaths per year in 2019, while cancers were responsible for 9.6 million deaths in 2017. Physical activity – particularly when it is moderate-intensity – is known to reduce the risk of cardiovascular disease and cancer, and the NHS recommends that adults do at least 150 minutes of moderate-intensity activity or 75 minutes of vigorous-intensity activity a week.
To explore the amount of physical activity necessary to have a beneficial impact on several chronic diseases and premature death, researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge carried out a systematic review and meta-analysis, pooling and analysing cohort data from all of the published evidence. This approach allowed them to bring together studies that on their own did not provide sufficient evidence and sometimes disagreed with each other to provide more robust conclusions.
In total, they looked at results reported in 196 peer-reviewed articles, covering more than 30 million participants from 94 large study cohorts, to produce the largest analysis to date of the association between physical activity levels and risk of heart disease, cancer, and early death.
The researchers found that, outside of work-related physical activity, two out of three people reported activity levels below 150 min per week of moderate-intensity activity and fewer than one in ten managed more than 300 min per week.
Broadly speaking, they found that beyond 150 min per week of moderate-intensity activity, the additional benefits in terms of reduced risk of disease or early death were marginal. But even half this amount came with significant benefits: accumulating 75 min per week of moderate-intensity activity brought with it a 23% lower risk of early death.
Dr Soren Brage from the MRC Epidemiology Unit said: “If you are someone who finds the idea of 150 minutes of moderate-intensity physical activity a week a bit daunting, then our findings should be good news. Doing some physical activity is better than doing none. This is also a good starting position – if you find that 75 minutes a week is manageable, then you could try stepping it up gradually to the full recommended amount.”
Seventy-five minutes per week of moderate activity was also enough to reduce the risk of developing cardiovascular disease by 17% and cancer by 7%. For some specific cancers, the reduction in risk was greater – head and neck, myeloid leukaemia, myeloma, and gastric cardia cancers were between 14 and 26% lower risk. For other cancers, such as lung, liver, endometrial, colon, and breast cancer, a 3–11% lower risk was observed.
Professor James Woodcock from the MRC Epidemiology Unit said: “We know that physical activity, such as walking or cycling, is good for you, especially if you feel it raises your heart rate. But what we’ve found is there are substantial benefits to heart health and reducing your risk of cancer even if you can only manage 10 minutes every day.”
The researchers calculated that if everyone in the studies had done the equivalent of at least 150 min per week of moderate-intensity activity, around one in six (16%) early deaths would be prevented. One in nine (11%) cases of cardiovascular disease and one in 20 (5%) cases of cancer would be prevented.
However, even if everyone managed at least 75 min per week of moderate-intensity physical activity, around one in ten (10%) early deaths would be prevented. One in twenty (5%) cases of cardiovascular disease and nearly one in thirty (3%) cases of cancer would be prevented.
