Year: 2022

Categories : Ageing Diet and NutritionTags :

Soluble Fibre is Associated with Lower Dementia Risk

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Source: Pixabay

Drawing on a decades-long cohort study, researchers in Japan have found that higher levels of dietary fibre, particularly soluble fibre, are associated with a lower risk of dementia.

Fibre is known to have vital importance for a healthy digestive system and also has cardiovascular benefits like reduced cholesterol. In a new study published in Nutritional Neuroscience, researchers have shown that a high-fibre diet is also associated with a reduced risk of developing dementia, adding to evidence that fibre is also important for a healthy brain.

“Dementia is a devastating disease that usually requires long-term care,” says lead author of the study Professor Kazumasa Yamagishi. “We were interested in some recent research which suggested that dietary fibre may play a preventative role. We investigated this using data that were collected from thousands of adults in Japan for a large study that started in the 1980s.”

Between 1985 and 1999, 3739 participants who were generally healthy and aged between 40–64 completed dietary information surveys. They were then followed up from 1999 until 2020, and it was noted whether they developed dementia that required care.

Participants were assigned into four groups according to the amount of fibre in their diets. They found that the groups who ate higher levels of fibre had a lower risk of developing dementia.

The team also examined whether there were differences for the two main types of fibre: soluble and insoluble fibres. Soluble fibres, found in foods such as oats and legumes, are important for the beneficial bacteria that live in the gut as well as providing other health benefits. Insoluble fibres, found in whole grains, vegetables, and some other foods, are known to be important for bowel health. The researchers found that the link between fibre intake and dementia was more pronounced for soluble fibres.

The team has some ideas as to what might underlie the link between dietary fibre and the risk of dementia.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” said Professor Yamagishi. “One possibility is that soluble fibre regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia. It’s also possible that dietary fibre may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels. The work is still at an early stage, and it’s important to confirm the association in other populations.”

Source: University of Tsukuba

Categories : Cardiovascular DiseaseTags :

Cough Suppressant Could Lead to New Arrhythmia Treatment

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Photo by cottonbro from Pexels

An over-the-counter cough suppressant can knock some heart cells out of arrhythmia, a discovery that could lead to a new treatment for long QT syndrome. The finding, which was published in Nature Cardiovascular Research, was made using stem cells from patients with the disorder.

The QT interval on an electrocardiogram (ECG) represents the duration of the ventricular action potential, and this physiologically correlates with the duration of the ventricular depolarisation and repolarisation. Cardiac events and fatal arrhythmias may occur when the QT interval is prolonged either congenitally or through acquired causes. In people with long QT syndrome, cardiac cells are not always ready to produce the next beat, a situation that can knock the heart out of its normal rhythm, which may be life-threatening. For many people with long QT, no treatment can correct the heart cells or prevent arrhythmia.

Using mice to investigate how human heart arrhythmias can be stopped is difficult, so Masayuki Yazawa, PhD at the University of Columbia, turned to patient-derived reprogrammed stem cells, which can be made into heart cells in the lab.

The road to the discovery began several years ago when Dr Yazawa found that heart cells in the lab would resume a normal rhythm when a certain enzyme was inhibited. But the drugs used to inhibit the enzyme also had other unintended effects, such as liver toxicity, so alternatives were needed.

Looking through published research, the team learned that the enzyme could be inhibited through an intermediary molecule inside heart cells called SIGMAR1. Further reading suggested that SIGMAR1 could be targeted by a cough suppressant, dextromethorphan.

Dr Yazawa’s team found that the cough suppressant, when added to heart cells, successfully prepared the heart cells for the next beat and soothed the cells’ irregular rhythm.

The cough suppressant reset heart cells from people with Timothy syndrome, a genetic disorder that also causes other heart abnormalities, and from people with more common forms of long QT syndrome.

Dr Yazawa cautioned that it’s premature to use dextromethorphan to treat long QT patients; the drug has a short half-life and would have to be used long term, which might still have unknown adverse side effects.

“But our study shows that drugs targeting SIGMAR1 have potential to treat a wide array of patients with long QT syndrome,” said Dr Yazawa, “and we will continue to look for better options.”

Source: Columbia University

Categories : Substance UseTags :

LSD Microdosing Study Shows no Benefit

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Photo by Bruce Christianson on Unsplash

Published in Addiction Biology, a study into the effects of LSD “microdosing” found no evidence to back up proponents’ claims that it can improve mood and cognitive function. 

The study’s lead author, Chicago University Professor Harriet de Wit, noted that the study doesn’t disprove microdosing’s possible benefits, and that more investigation is needed. The study does show that taking small doses of LSD is safe. Prof De Wit said the findings demonstrate the important role clinicians can play when it comes to therapeutics claims about recreational drugs.

“These drugs are already being used out in the world, and it’s important for us to test them under controlled conditions, ensure their safety and see whether there’s some validity to the benefits people claim,” she said. “That’s something that has been missing from the conversation.”

The researchers studied the effects of four repeated low doses of LSD, administered under lab conditions every three to four days. One group of participants received 13 micrograms of the drug, a second group received 26 micrograms, and the third received a placebo. To put these low doses into context, the doses of LSD that are used to “trip” or to get high are typically 100–200 micrograms, she said.

LSD was chosen for the study because it’s the most commonly used psychedelic drug in microdosing.

Participants received the drugs during five-hour, supervised laboratory sessions. They also attended a drug-free follow-up session three to four days after the last dose. Participants were not told what kind of drug was being tested in the study – whether it was a stimulant, a tranquiliser or a hallucinogen – or that the study was about microdosing.

“We removed any expectations that this was a psychedelic drug,” Prof de Wit explained. “Because in the real world, people’s expectations can strongly influence their responses.”

To assess their mood and mental performance, the participants completed cognitive and emotional tasks both during the drug administration sessions and at the drug-free follow-up session. Some participants who received the higher dose reported feeling a modest “high” during the drug sessions, but the effects were mild.

The drug did not improve mood or affect participants’ performance on cognitive tests, either during the drug sessions or at the follow-up session.

Prof De Wit said the results came as a disappointing surprise. “Because so many people claim to have experienced benefits from microdosing, we expected to document some kind of beneficial effect under laboratory conditions,” she said.

Neurobiological reasons had also suggested that LSD might improve mood, because LSD acts through serotonin receptors, where traditional antidepressants are known to act.

“We can’t say necessarily that microdosing doesn’t work,” Prof de Wit said. “All we can say is that, under these controlled circumstances, with this kind of participant, these doses, and these intervals, we didn’t see a robust effect.”

People who microdose often have strong expectations of beneficial effects. “It is possible that these expectations contribute to the apparent benefits, or they may interact with the pharmacological effect of the drug,” she said.

LSD was confirmed to be safe, an unsurprising find which is in line with previous human and animal studies.

In fact, de Wit noted, participants appeared to build a tolerance to LSD over the course of the study, with the strongest “high” reported at the first session, and the perception of a drug effect diminishing at each subsequent session. That’s a good sign because it confirms the drug does not stay in the body or accumulate over time, she said.

Getting authorisation to use a controlled substance made the experiment challenging, as did the participants’ necessary time commitment. However, Prof de Wit emphasised the importance of such research, especially as practices like microdosing become commercialised.

“There are a lot of companies getting into the drug business, either with psychedelic drugs, or drugs like cannabidiol,” she noted. “And really there’s not very much empirical support to back up their claims. So, I think we have a responsibility to investigate and validate the claims.”

Source: University of Chicago

Categories : COVIDTags :

India’s True Pandemic Death Toll Likely Over Three Million

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FIG. 1. Percentages of adults reporting daily death in household, expected percentage in 2020, and daily confirmed COVID deaths in India, 1 June 2020 to 1 July 2021. COVID Tracker deaths (red line, left vertical scale) represent COVID deaths reported daily (smoothed for rolling 7-day averages) at age 35 or older, less a subtraction value of 0.59% to represent nonhousehold reporting. Expected all-cause deaths (grey dashed line, left vertical scale) per year of 3.4% (see text), with 7-day smoothed weekly adjustment from variation observed among 480,000 deaths in the Million Death Study from 2004 to 2014. Confirmed COVID deaths (blue bars, right vertical scale) are daily reports from Covid19india.org (2).
Credit: DOI: 10.1126/science.abm5154

An updated estimate for COVID mortalities in India puts the true number at over three million, which is so much higher than the official estimate of around a million that it would raise the World Health Organization’s official global death toll by 50%.

When the COVID Delta wave hit India over early to mid-2021, hospitals were filled beyond capacity, oxygen ran out, and community networks for tending to the dead were overwhelmed. At the time, government reporting put the death toll at under a million.

However, other sources estimated that the toll was far worse than this, likely in the millions. A more accurate measure of COVID mortality in India puts that number at 3.2 million people, according to a paper published in Science. 

“The analyses find that India’s cumulative COVID deaths by September 2021 were six to seven times higher than reported officially,” the international team of researchers wrote.

“You have to put that into context,” said Associate Professor of Economics Paul Novosad, co-author of the paper. “At the time that we were writing this, India was reporting about half a million official COVID deaths, the World Health Organization was reporting about 4 to 5 million COVID deaths globally, so just this adjustment – just correctly counting the deaths in India – is going to raise the global mortality count of COVID by almost 50%.”

The team looked at all-causes mortality from an independent survey of 140 000 adults, and from two government data sources including deaths reported in health facilities and registered deaths in 10 Indian states. Comparing these to previous years without COVID, they found that total deaths increased by 26% to 29% in the COVID period compared to total deaths in past years. This range was consistent across separate data sources, the researchers wrote.

“We’re triangulating on this number from a lot of different directions and have broad agreement regarding the range that we’re finding,” said Novosad.

Novosad’s work incorporates many novel types of data, including measures of well-being generated from satellite images, data collected by government programs, and archival administrative records not previously used for policy design. His research lab, which focuses on India, has created an open source data platform to support socioeconomic research in India and the developing world.

“A large part of my research agenda is based on finding new, 21st-century data sources and mobilising them for better research and policy,” he said.

Novosad believes this work can help answer many  critical questions about how governments and organisations can respond to the global pandemic.

“The decisions you make are better if they’re based on true facts about the world. If you don’t have data, then you just have to work on stories and impressions,” he said. “We need an empirical foundation for this kind of work.”

Source: Dartmouth College

Categories : Diseases, Syndromes and Conditions GeneticsTags :

A Life-changing Genetic Cure for Sickle Cell Patient

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Sickle cell disease occurs in people who inherit two copies of the sickle cell gene, one from each parent. This produces abnormal haemoglobin, called haemoglobin S. Credit: Darryl Leja, National Human Genome Research Institute, National Institutes of Health

Jimi Olaghere, who had suffered all his life from the chronic pain of sickle cell disease, recently received a genetic cure decades sooner than he would have believed possible.

Mr Olaghere is one of the first seven sickle cell patients who received a new gene-editing treatment going through its first clinic trials in the US. “It’s like being born again,” he said, adding that it has changed his life. “When I look back, it’s like, ‘Wow, I can’t believe I lived with that.'”

Mr Olaghere, 36 said: “You always have to be in a war mindset, knowing that your days are going to be filled with challenges.”

Sickle cell disease is caused by a mutated gene that results in abnormal haemoglobin, leading to blood cells becoming more rigid and taking on their characteristic sickle shape. These malformed cells often get stuck in blood vessels, giving rise to ischaemias and an increase in cardiovascular disease risk and organ damage. Mr Olaghere may need a hip replacement due to avascular necrosis.

The disease also causes chronic pain, which he likened to “shards of glass flowing through your veins or someone taking a hammer to your joints.”

Severe pain episodes known as crises are the hallmark of sickle cell disease. For years, Mr Olaghere was hospitalised on a monthly basis. Winters worsened the problem as the cold restricted surface blood vessels, increasing the risk of blockages. He moved to a warmer city, and became a tech entrepreneur as he didn’t think any employer would be sympathetic to going to the hospital so often.

His family urged him to participate in clinical trials or receive a bone marrow transplant. However, he thought it would take too much time and instead pinned his hopes on DNA editing “in the future, probably 20 to 50 years from now”.

But in 2019 he read about a new gene editing therapy and emailed the medical team right away. When he learned he was accepted, he said it was “the best Christmas present ever”. As the pandemic hit and flights were cancelled, he was still able to make the four-hour drive for treatment appointments.
In order to genetically edit his stem cells the stem cells were flushed out of his bone marrow and into the bloodstream for collection.

“You sit there for eight hours and this machine is literally just sucking all the blood out of you,” he said.

The process left him physically and mentally drained, and still needed  blood transfusions. Mr Olaghere had to go through this process, the most difficult of all for him, four times. 

The key to the treatment lies not in correcting the genetic defect that produces the cell but rather sidestepping it by getting the body to use an alternative: foetal haemoglobin 

Ordinarily, at around 40 weeks of pregnancy, a genetic switch called BCL11A is flipped and the body starts producing adult haemoglobin – which is the only form affected by sickle cell disease. 

“Our approach is to turn that switch off and increase the production of foetal haemoglobin again, basically turning the clock back,” explained Dr Haydar Frangoul, who treated Mr at the Sarah Cannon Research Institute.

Mr Olaghere’s stem cells were sent to Vertex Pharmaceuticals’ laboratories for genetic editing. By September 2020, the engineered cells were ready to be infused into his body. “It was the week of my birthday, actually. So it was almost like getting a new life,” he recalled.

The original faulty stem cells that remained in his body were killed off with chemotherapy, and then genetically engineered replacements were infused into his body to produce sickle-free blood.

“I remember waking up without any pain and feeling lost,” he said. “Because my life is so associated with pain, it’s just a part of who I am. It’s weird now that I don’t experience it any more.'”

Dr Frangoul said that the first seven patients’ results have been “nothing short of amazing” and represented a “functional cure” for their disease.
“What we are seeing is patients are going back to their normal life, none have required admission to hospital or doctor visits because of sickle cell related complications,” Dr Frangoul said.

So far, the genetic technique has been conducted on 45 patients with either sickle cell disease or beta thalassaemia. However, the data are still being gathered.

Source: BBC News

Categories : COVID Expert OpinionTags :

An Estimated 70% of South Africans Have Had COVID

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Image by Quicknews

Writing for GroundUp, Dr Alex Welte unpacks the results of the latest blood donor survey, which suggests that some 70% of South Africans have had a COVID infection.

The South African National Blood Service (which handles the blood supply for eight provinces) and the Western Cape Blood Service have been testing some donors for Covid antibodies over the last year or so. This has contributed to our understanding of how many people have been infected by SARS-CoV-2 (the virus that causes Covid), and what proportion of infections lead to death. It may help us plan for future waves, though exactly how is complicated.

On the assumption that another wave towards the end of 2021 was nearly inevitable – but before we all heard about omicron – it was decided to perform more such testing in early November. The numbers are now out.

The headline results are:

  • Overall about 80% of black donors had previously had Covid, and 40% of white donors.
  • There is no meaningful variation between age groups and sexes.
  • This latest survey did not include Western Cape data.
  • The test used does not detect the antibodies produced in response to vaccination, so this really is an estimate of people who have been infected.

While blood donors are not perfectly representative of the country’s population, we can take into account differences between the racial breakdown of the donor population and the racial breakdown of the general population. This means that our face-value national estimate is that about 70% of people had been infected before the omicron wave hit.

Since then we’ve had the omicron wave. We would very much like to know how many people are infected now, but there’s really no simple way to derive this number. Researchers are now updating their models with this additional piece of data, and we may see some estimates soon.

With that caution, here is my back-of-the-envelope estimate:

  • Omicron seems to have little trouble infecting people who have been infected by other variants, though there is some protection from prior infection and vaccination.
  • By late last year, quite a bit more than half the population had already had a prior infection.
  • Hence, I estimate that about half of the omicron wave infections were in previously uninfected individuals.
  • Given the infection detection rate estimates from previous waves, and a number of plausible sources of possible variation in this rate, I estimate the detection rate at about 1 in 10.
  • Given the roughly 700 000 cases reported between mid November and mid February, we get an estimate of 7 million cases, and therefore 3.5 million new infections.
  • Given our population of about 60 million, this is roughly an additional 6%.
  • Bottom line: it’s not crazy to estimate that about three-quarters of South Africans have by now been infected. But I would not be surprised if serious models come up with even higher estimates.

A troubling result of the survey is that once more it shows the serious racial disparities in South Africa. I don’t know if this carried over to the omicron wave. Estimating the racial breakdown of infection after omicron depends in a complicated way on variations in housing, lifestyle, access to vaccination, and all the usual factors that shape daily life in our country.

Dr Welte helped design and implement the blood donor survey.

Source: GroundUp

Categories : Neurodegenerative DiseasesTags :

Peptide Discovery Could Halt Nerve Degeneration

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A healthy neuron.
A healthy neuron. Credit: NIH

Promising results have been found in the quest for a treatment to halt nerve cell degeneration in disorders like Parkinson’s disease, by preventing their mitochondria from breaking apart with a particular peptide.

The research, published in Brain, examined how the long axons that carry messages between nerve cells in the brain can break down, which causes increasingly worse tightening of the leg muscles, leading to imbalance and eventually paralysis, in addition to other symptoms.

Animal studies have shown it may be a problem with the mitochondria that leads to the axons breaking down or not growing long enough. Since studying human nerve cells is difficult, the researchers made use of human stem cells they modified to become nerve cells with the genetic disorder for a particular type of hereditary spastic paraplegia.

“What we found was that the mitochondria in these cells were breaking apart, what we call mitochondrial fission, and that caused the axons to be shorter and less effective at carrying messages to the brain,” study leader Prof Xue-Jun Li said. “We then looked at whether a particular agent would change the way the nerve cells function — and it did. It inhibited the mitochondrial fission and let the nerve cells grow normally and also stopped further damage.”

What this means for the thousands of people affected by this type of genetic disorder is that this peptide could prove to be useful for a drug or other therapy to stop the nerve cells from becoming damaged or possibly even reverse the course of the damage. Additionally, gene therapy could also prevent mitochondrial damage, the researchers suggested, which would provide another strategy to reverse the nerve damage.

Source: University of Illinois Chicago

Categories : Implants and Prostheses UncategorizedTags :

Recipients of Bionic Eyes Blindsided by Obsolescence

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Source: Daniil Kuzelev on Unsplash

After the manufacturer of a bionic eye ended support, hundreds of recipients of the vision-improving implants have been left without support – “literally in the dark”, as one of them put it.

IEEE Spectrum, which first broke the story, reported that Second Sight discontinued its retinal implants in 2019. The retinal implants serve as the source of artificial vision for the users.

The publication wrote that the firm’s focus is currently on developing a brain implant known as the Orion, which also provides artificial vision. However, it only offers very limited support to the 350 or so who have the now-obsolete Argus II implants.

The system consists of a camera mounted on glasses worn by the user, which transmits video to a video processing unit (VPU), which then encodes the images into arrays of black and white pixels. The VPU then relays the pixel to an electrode array behind the retina, which creates flashes of light corresponding to the white pixels. The technology has had a long and costly road from experiment to product, starting with a lab experiment in the 1990s where stimulation of a single electrode in the retina was discovered to create a visible flash of light perceived by a blind patient. It is hugely expensive, with an estimated cost of $150,000 (R2.25 million) even before the surgery and post-surgery training. 

Implantation surgery typically takes a few hours, followed by training to help users interpret the new optical input from their implants. It is not a replacement for sight; rather it is more like a new sense. Users of the system see fleeting changes of grey which some can then use to assist with basic locomotion. However, the technology is still crude and not all benefit to the same degree. While some can make out the stripes on a pedestrian crossing, others never achieve that level of ability.

The technology also comes with some risk. In the postapproval period, 17% experienced adverse events, though this was an improvement over the 40% in the preapproval period. Since the implant can interfere with MRI scans, some have had to consider removal.

IEEE Spectrum contacted a number of patients, who voiced concern over their future. One patient, Ross Doer, said he was delighted when Second Sight told him in 2020 he was eligible for software upgrades. Yet, he heard troubling rumours. When he called his Second Sight vision-rehab therapist, “She said, ‘Well, funny you should call. We all just got laid off,’ ” he recalled. “She said, ‘By the way, you’re not getting your upgrades.’ ”

“Those of us with this implant are figuratively and literally in the dark,” he said.

Second Sight, when contacted by the publication, said that it had to reduce its workforce because of financial difficulties, and though it attempted to provide “virtual support” was unable to assist with repairs or replacements.
Benjamin Spencer, one of the six patients to receive the new Orion implant, said that it was “amazing” and he was able to see his wife for the first time. But knowing what he does now about Second Sight makes him apprehensive, and plans to have his implant removed at the end of the study period.

Speaking to the BBC, Elizabeth M. Renieris, professor of technology ethics at the University of Notre Dame, in the US, described the development as a cautionary tale.

“This is a prime example of our increasing vulnerability in the face of high-tech, smart and connected devices which are proliferating in the healthcare and biomedical sectors,” she said.

“These are not like off-the-shelf products or services that we can actually own or control. Instead we are dependent on software upgrades, proprietary methods and parts, and the commercial drivers and success or failure of for-profit ventures.”

She added that in future, ethical considerations concerning such technology should include “autonomy, dignity, and accountability”.

Source: IEEE Spectrum

Categories : Cardiovascular DiseaseTags :

New Blood Thinners from Tick Saliva

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Source: Wikimedia CC0

Researchers looking for new anti-clotting drugs have discovered a unique class of medications that act as blood thinners by inhibiting an enzyme in the genes of tick saliva.

The study, published in Nature Communications, focused on novel direct thrombin inhibitors (DTI) from tick salivary transcriptomes, or messenger RNA molecules expressed by an organism. As a result of  the research, there are now new anticoagulant medications that can be developed for the treatment of patients with a variety of coronary issues, including heart attacks.

“Interest in ticks as a model for developing drugs that prevent blood clotting – [often] the cause of heart attacks and strokes – is firmly rooted in evolutionary biology,” said Professor Richard Becker, a co-author of the study.

“Analysis of backbone structures suggest a novel evolutionary pathway by which different blood clot inhibiting properties evolved through a series of gene duplication events. Comparison of naturally occurring blood clot inhibitors of differing tick species suggests an evolutionary divergence approximately 100 million years ago.”

Prof Becker and his international colleagues discovered DTIs from tick salivary transcriptomes and optimised their use as a pharmaceutical. The most potent is a key regulating enzyme in blood clot formation with very high specificity and binding capacity that is almost 500 times that of bivalirudin, a drug used during a typical nonsurgical procedure used to treat narrowing of the coronary arteries. Those minimally invasive procedures are performed in roughly 1 million persons yearly in the United States.

“Despite their greater ability to reduce the incidence of the formation of blood clots, the drugs demonstrated less bleeding, achieving a wider therapeutic index in nonhuman models,” Becker says. “The higher potency of the drug means it’s not necessary to use a lot of it in treating patients, which holds the cost of goods and manufacturing down.”

According to Prof Becker, tick saliva, as in other blood-feeding such as mosquitoes, contains pharmacological and immunological active compounds, which modulate immune responses and induce antibody production. This research leveraged an understanding of tick-host interactions and antibody formation.

“The holy grail of anticoagulant therapy has always been specificity, selectivity, efficacy and safety,” said Prof Becker. “Clinician-scientists must have the training and an environment that embraces asking questions and finding solutions, including those potential found deep within nature. An ability to both measure and adjust the drug dose and rapidly reverse its effects is particularly important for safety purposes. The next step is to complete pharmacology, toxicology, drug stability and other important regulatory steps before conducting clinical trials in humans.”

Source: University of Cincinnati

Categories : CancerTags :

New Recommendations for Earlier Breast Cancer MRI Screening

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This screening MRI detected a very small cancer (circled) in the patient’s breast.
Credit: Dr. Kathyrn Lowry

Annual MRI screenings starting at ages 30 to 35 may slash breast-cancer mortality by more than 50% among women with genetic changes in three genes, according to a study published in JAMA Oncology.

The pathogenic variants are in the ATM, CHEK2 and PALB2 genes – which collectively are as prevalent as the much-reported BRCA1/2 gene mutations. The study authors state that their findings support earlier MRI screening in these women.

“Screening guidelines have been difficult to develop for these women because there haven’t been clinical trials to inform when to start and how to screen,” said lead author Dr Kathryn Lowry.

The work was a collaboration of the Cancer Intervention and Surveillance Modeling Network (CISNET), the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium, and the Breast Cancer Surveillance Consortium.

To arrive at their model, the researchers input age-specific risk estimates from CARRIERS involving some 64 000 women and recent published data for screening performance.

“For women with pathogenic variants in these genes, our modeling analysis predicted a lifetime risk of developing breast cancer at 21% to 40%, depending on the variant,” Dr Lowry said. “We project that starting annual MRI screening at age 30 to 35, with annual mammography starting at age 40, will reduce cancer mortality for these populations of women by more than 50%.”

The simulations compared the combined performance of mammography and MRI against mammography alone, and projected that annual MRI conferred significant additional benefit to these populations.

“We also found that starting mammograms earlier than age 40 did not have a meaningful benefit but increased false-positive screens,” Dr Lowry added.

Results from CISNET models have informed past guidelines, including the 2009 and 2016 U.S. Preventive Services Task Force recommendations for breast cancer screening in average-risk women.

“Modelling is a powerful tool to synthesise and extend clinical trial and national cohort data to estimate the benefits and harms of different cancer control strategies at population levels,” said senior author Dr Jeanne Mandelblatt.

The study projected about four false-positive screening results and one to two benign biopsies per woman over a 40-year screening span, the authors noted.

To get any benefit from genetic susceptibility-based screening guidelines, a woman would have to know beforehand that she carries the gene, yet most often a genetic test panel is done after a positive cancer result – too late for any benefit.

“People understand very well the value of testing for variants in BRCA1 and BRCA2, the most common breast cancer predisposition genes. These results show that testing other genes, like ATM, CHEK2, and PALB2, can also lead to improved outcomes,” said senior author Dr Mark Robson.

The researchers hope their analysis will aid the National Comprehensive Cancer Network (NCCN), the American Cancer Society and other organizations that issue guidance for medical oncologists and radiologists.

“Overall what we’re proposing is slightly earlier screening than what the current guidelines suggest for some women with these variants,” said senior author Professor Allison Kurian. “For example, current NCCN guidelines recommend starting at age 30 for women with PALB2, and at 40 for ATM and CHEK2. Our results suggest that starting MRI at age 30 to 35 appears beneficial for women with any of the three variants.”

Source: University of Washington