Category: Academic Analysis

Source: The Conversation – UK – By Martin L. Olsson, Medical Director of the Nordic Reference Laboratory for Blood Group Genomics, Region Skåne & Professor of Transfusion Medicine, Head of the Division, Lund University

In a routine blood test that turned extraordinary, French scientists have identified the world’s newest and rarest blood group. The sole known carrier is a woman from Guadeloupe whose blood is so unique that doctors couldn’t find a single compatible donor.

The discovery of the 48th recognised blood group, called “Gwada-negative”, began when the woman’s blood plasma reacted against every potential donor sample tested, including those from her own siblings. Consequently, it was impossible to find a suitable blood donor for her.

Most people know their blood type – A, B, AB or O – along with whether they are Rh-positive or negative. But these familiar categories (those letters plus “positive” or “negative”) represent just two of several dozens of blood group systems that determine compatibility for transfusions. Each system reflects subtle but crucial differences in the proteins and sugars coating our red blood cells.

To solve the mystery of the Guadeloupian woman’s incompatible blood, scientists turned to cutting-edge genetic analysis. Using whole exome sequencing – a technique that examines all 20,000-plus human genes – they discovered a mutation in a gene called PIGZ.

This gene produces an enzyme responsible for adding a specific sugar to an important molecule on cell membranes. The missing sugar changes the structure of a molecule on the surface of red blood cells. This change creates a new antigen – a key feature that defines a blood group – resulting in an entirely new classification: Gwada-positive (having the antigen) or -negative (lacking it).

Using gene editing technology, the team confirmed their discovery by recreating the mutation in a lab. So red blood cells from all blood donors tested are Gwada-positive and the Guadeloupean patient is the only known Gwada-negative person on the planet.

The implications of the discovery extend beyond blood transfusions. The patient suffers from mild intellectual disability, and tragically, she lost two babies at birth – outcomes that may be connected to her rare genetic mutation.

The enzyme produced by the PIGZ gene operates at the final stage of building a complex molecule called GPI (glycosylphosphatidylinositol). Previous research has shown that people with defects in other enzymes needed for GPI assembly can experience neurological problems ranging from developmental delays to seizures. Stillbirths are also common among women with these inherited disorders.

Although the Caribbean patient is the only person in the world so far with this rare blood type, neurological conditions including developmental delay, intellectual disability and seizures have been noted in other people with defects in enzymes needed earlier in the GPI assembly line.

The Gwada discovery highlights both the marvels and challenges of human genetic diversity. Blood groups evolved partly as protection against infectious diseases (many bacteria, viruses and parasites use blood group molecules as entry points into cells). This means your blood type can influence your susceptibility to certain diseases.

But extreme rarity creates medical dilemmas. The French researchers acknowledge they cannot predict what would happen if Gwada-incompatible blood were transfused into the Guadeloupian woman. Even if other Gwada-negative people exist, they would be extremely difficult to locate. It is also unclear if they can become blood donors.

This reality points towards a futuristic solution: lab-grown blood cells. Scientists are already working on growing red blood cells from stem cells that could be genetically modified to match ultra-rare blood types. In the case of Gwada, researchers could artificially create Gwada-negative red blood cells by mutating the PIGZ gene.

A growing field

Gwada joins 47 other blood group systems recognised by the International Society of Blood Transfusion. Like most of these blood-group systems, it was discovered in a hospital lab where technicians were trying to find compatible blood for a patient.

The name reflects the case’s Caribbean roots: Gwada is slang for someone from Guadeloupe, giving this blood group both scientific relevance and cultural resonance.

As genetic sequencing becomes more advanced and widely used, researchers expect to uncover more rare blood types. Each discovery expands our understanding of human variation and raises fresh challenges for transfusion and other types of personalised medicine.

Martin L Olsson is a Wallenberg Clinical Scholar who receives research funding from Knut and Alice Wallenberg Foundation (grant no. 2020.0234). He holds other major grants from the Swedish Research Council (grant no. 2024-03772), the Novo Nordisk Foundation (grant no. NNF22OC0077684) and the Swedish government funds to university healthcare for clinical research (ALF grant no. 2022.0287). He is also a member of the International Society of Blood Transfusion (ISBT)’s Working Party on Red Cell Immunogenetics and Blood Group Terminology.

Jill Storry receives funding from the Swedish Research Council (grant no. 2024-03772). She is affiliated with, and the current senior Vice-President, of the International Society of Blood Transfusion, as well as a member of the society’s Working Party on Red Cell Immunogenetics and Blood Group Terminology.

– ref. Gwada-negative: the rarest blood group on Earth – https://theconversation.com/gwada-negative-the-rarest-blood-group-on-earth-260155

Source: The Conversation – UK – By Leah McLaughlin, Research Fellow in Health Services, Bangor University

What does it mean to save a life – and what does it cost? In The Story of a Heart, Rachel Clarke answers this not with slogans or sentiment, but with quiet, searing honesty. This book, which won this year’s Women’s prize for non-fiction, is about organ donation, yes, but it’s also about family, grief, love, courage, and the astonishing edges of human experience.

At its centre are two children: Max Johnson, a healthy, active nine-year-old whose heart suddenly begins to fail, and Keira Ball, another nine-year-old – vibrant, horse-loving, full of life who tragically dies in a car accident. In a moment of unimaginable grief, Keira’s parents donate her organs. Her heart goes to Max.

A child dies. A child lives.

That is the simple, brutal, beautiful truth this book never looks away from. But Clarke does more than tell the story of heart. She immerses us in it – every breath, every monitor beep, every unbearable choice.

I read this as a health services researcher who has spent years working in the emotionally complex, ethically charged, and often hidden world of organ donation. My work explores how families navigate these unimaginable scenarios, particularly in the context of recent legislative change. Clarke’s account captures, with rare precision and compassion, the silences, the emotional labour of clinicians, and the profound weight of choice that families like Keira’s carry.

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As both a doctor and a mother, Clarke brings sensitivity to every page. We feel Max’s steady decline: the exhaustion, the fear, the silence that descends as even the doctors grow unsure. We witness Keira’s final hours, the heroic efforts to save her, and the moments where unbearable grief oscillates between hope and despair, eventually giving way to a different kind of gift.

There are no easy heroes in this story, only ordinary people facing the unthinkable with extraordinary grace. Clarke brings them to life with aching clarity: the cardiologist who, in the dim light of a hospital room, sketches Max’s failing heart on a napkin so his mother can understand what words can’t explain; the ICU nurse who stays long after her shift ends, gently brushing the hair of a child who will never wake up; the donation nurse who enters a family’s darkest hour not with answers, but with quiet presence and unwavering care; the surgeon who steadies his hands – and his heart – when every second matters.

And in the chaos of resuscitation, amid alarms and broken bodies, a teddy bear is tucked beneath Keira’s arm: “Someone in the crash team has seen Keira not simply as a body, inert and unresponsive, but as a vulnerable child in need of compassion.”

The Story of a Heart is also a book about history. It’s not just about one child’s transplant, but about medicine, surgery, and the heart itself. Clarke weaves in the stories of early transplant pioneers, accidental discoveries, and the scientific stumbles and breakthroughs that built modern practice. She brings it all to life with a storyteller’s flair, making science feel intimate, alive, and deeply human.

What the heart means

What sets the heart apart, Clarke reminds us, is not just its function, but its symbolism. No other organ holds such emotional weight. “Hearts sing, soar, race, burn, break, bleed, swell, hammer and melt,” she writes. They are not just organs, they are vessels for our hopes, fears and deepest longings.

Clarke shows how, across history, the heart was seen as the source of emotion, morality – even the soul – and how that deep humanism still pulses through our language and culture today. We have our hearts broken, wear our hearts on our sleeves, and as Clarke puts it: “When trying to express our truest and most sincere selves, we do so by saying we speak from the heart, or about all that our heart desires.”

But what makes The Story of a Heart so exceptional is its emotional truth. Clarke never shies away from the pain. Max’s parents watch their son fade, terrified to even touch him. Keira’s father buys her a pink princess dress for her funeral. Max, wired to machines, records a goodbye message; we learn later he even tried to take his own life. And yet, there is light.

Keira’s sisters climb into bed with her, painting her nails and sliding Haribo sweet rings onto her fingers. Then comes a moment so clear, so quietly astonishing, it takes everyone’s breath away. Katelyn, Keira’s older sister, turns to the doctor and asks, with calm, steady eyes: “Can we donate her organs?”

This isn’t a clinical decision or a well-rehearsed conversation. It is an unprompted act of extraordinary love. These moments – fragile, generous, profoundly human – are the true beating heart of Clarke’s book.

From there, we are guided into a world so few know and even fewer ever witness: the quiet choreography that carries a gift of life from one person to another. What Katelyn sets in motion with just five words unfolds with such precision, that reading it feels like witnessing a kind of living magic.

The aftermath is just as moving. Max recovers quickly, walks again, laughs again. The two families meet. There are no big speeches, just quiet awe. And beyond that: a law is passed. Max and Keira’s Law brings in an opt-out system of donation in England. Two children. One legacy. A country changed.

And still, Clarke doesn’t let us forget the hard truths. Not every child survives. Not every family gets a miracle. Transplants are fragile. But in that fragility, she shows us, is the real miracle. Max goes fishing with his dad, the sky glows orange – Keira’s favourite colour. That is enough.

At the moment organ donation consent rates for children are declining in the UK, and there are more children on the transplant wait list than ever before. The Story of a Heart asks us to see the children, the families, and the quiet acts of love behind every donation. It’s a powerful reminder that the greatest gifts are often given in the darkest hours.

This book will break your heart – and fill it up again. It’s not just essential reading for anyone interested in organ donation and transplant. It’s essential reading for anyone who has ever loved.

This article features references to books that have been included for editorial reasons, and may contain links to bookshop.org. If you click on one of the links and go on to buy something from bookshop.org The Conversation UK may earn a commission.

Leah McLaughlin does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

– ref. The Story of a Heart by Rachel Clarke is a powerful account of one child’s gift to another – https://theconversation.com/the-story-of-a-heart-by-rachel-clarke-is-a-powerful-account-of-one-childs-gift-to-another-260611

Source: The Conversation – UK – By Ernestine Gheyoh Ndzi, Senior Lecturer at York Business School, York St John University

The recent launch of a government review into parental leave and pay in the UK is a hugely welcome development. In order to bring about meaningful change, it must challenge the fundamental issue at the heart of current parental leave laws. They are strongly influenced by, and so perpetuate, gender norms that see women as caregivers and fathers as breadwinners.

Parents in the UK can take maternity leave, paternity leave and shared parental leave in the first year of their child’s life. While these allowances provide parents with support, the support is disproportionate in how it is split between mothers and fathers. Although gender roles have evolved significantly, UK policies lag behind.

Mothers and fathers are equal parents and have equal parenting responsibilities. However, mothers are allowed up to 52 weeks of maternity leave, while fathers are only entitled to two weeks of statutory paternity leave.

The introduction of shared parental leave in 2015 was welcomed as a positive step towards gender equality – but it has failed in this aim.

There are significant barriers stopping fathers from benefiting fully from the legislation. Parents can share up to 50 weeks of leave between them. But because mothers are entitled to a year of leave, the policy requires mothers to act as gatekeepers. The mother determines if the father can share the leave and how long she is willing to give up for the father.

Consequently, fathers have no autonomy or independence to take parental leave at a time that is important to them and their babies – and they may be reluctant to deprive the mother of leave she is entitled to.

What’s more, while maternity and paternity leave is well known and the process relatively straightforward, shared parental leave has been criticised for its complexity. Parents that have explored shared parental leave have found the policy and process incredibly complex because some employers still don’t understand how it works and so are unable to support parents.

The problems with the policy have affected its uptake. Only 5% of fathers take any shared parental leave.

Financial implications

Another problem that affects all three policies is the pay. While the UK has a generous maternity leave allowance of 52 weeks, this is not accompanied by a decent financial allowance.

Although employers can set more generous terms, the law requires only the first six weeks of maternity leave to be paid at 90% of the mother’s salary. This is followed by 33 weeks at statutory pay of £187.18 and 13 weeks of no pay. The two weeks of paternity leave are paid at the statutory rate of £187.18, or 90% of the father’s average weekly earnings (whichever is lower).

And while shared parental leave allows the mother to split 50 weeks of leave with her partner, a significant period of this is unpaid. Out of these 50 weeks, parents can share 37 weeks of pay at statutory rate and the rest of the leave would be unpaid.

Mothers have returned to work early because financially they cannot afford to stay longer on maternity leave – a problem compounded by the rising cost of living. Fathers sometimes opt to take annual leave rather than paternity leave because of the low pay.

The same reason applies to shared parental leave because parents cannot afford to both be off at the same time or different times on the statutory rate. While the policies are well intended, there is no financial incentive for parents to take it.

Finances have a significant impact on parental leave choices. The government review should enhance parental leave pay to encourage and support parents, particularly fathers.

Impact on careers

The implications for parents’ careers also need to be considered. While parental leave should not affect the career aspirations or progressions of the parents, my research demonstrates otherwise. Mothers have been bullied, refused opportunities, and have felt forced to leave their jobs.

Research also shows that fathers have concerns about their careers when considering parental leave. While it is illegal for an employer to discriminate against a parent for taking parental leave, this remains an area of concern.

My research has demonstrated that some fathers consider shared parental leave as a “luxury” they cannot afford. They feel they need to work hard to demonstrate their commitment to their job. Equal parenting policies would support women’s careers and encourage fathers to take up more family responsibilities without fear of repercussions.

The last point to consider – and one that often goes overlooked – is that how parents choose to feed their baby may have an effect on their decisions to take parental leave. Babies can be breastfed, formula fed or a mixture of both breast and formula feeding. If the parents make the decision to breastfeed – a choice recommended by the World Health Organisation – this may affect the mother’s decision on how much leave she takes.

Employers have legal obligations to carry out risk assessments for breastfeeding mothers and make reasonable adjustments on specific health and safety guidelines. However, a general policy that covers the wider needs of breastfeeding mothers and offers them more support at work should be implemented.

My research shows that mothers may prefer to take more maternity leave to enable them to breastfeed.

The parental leave review shouldn’t miss the opportunity to introduce breastfeeding policies that ensure mothers are properly supported in the workplace – as well as making sure that both mothers and fathers have the opportunity to prioritise caring and their careers.

Ernestine Gheyoh Ndzi does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

– ref. Parental leave in the UK isn’t working – here’s what needs to change – https://theconversation.com/parental-leave-in-the-uk-isnt-working-heres-what-needs-to-change-209661

Source: The Conversation – UK – By Tom Harper, Lecturer in International Relations, University of East London

As the 14th Dalai Lama celebrates his 90th birthday with thousands of Tibetan Buddhists, there’s already tension over how the next spiritual leader will be selected. Controversially, the Chinese government has suggested it wants more power over who is chosen.

Traditionally, Tibetan leaders and aides seek a young boy who is seen as the chosen reincarnation of the Dalai Lama. It is possible that after they do this, this time Beijing will try to appoint a rival figure.

However, the current Dalai Lama, who lives in exile in India, insists that the process of succession will be led by the Swiss-based Gaden Phodrang Trust, which manages his affairs. He said no one else had authority “to interfere in this matter” and that statement is being seen as a strong signal to China.

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Throughout the 20th century, Tibetans struggled to create an independent state, as their homeland was fought over by Russia, the UK and China. In 1951, Tibetan leaders signed a treaty with China allowing a Chinese military presence on their land.

China established the Tibetan Autonomous Region in 1965, in name this means that Tibet is an autonomous region within China, but in effect it is tightly controlled. Tibet has a government in exile, based in India, that still wants Tibet to become an independent state.

This is a continuing source of tension between the two countries. India also claims part of Tibet as its own territory.

Beijing sees having more power over the selection of the Dalai Lama as an opportunity to stamp more authority on Tibet. Tibet’s strategic position and its resources are extremely valuable to China, and play a part in Beijing’s wider plans for regional dominance, and in its aim of pushing back against India, its powerful rival in south Asia.

Tibet provides China with a naturally defensive border with the rest of southern Asia, with its mountainous terrain providing a buffer against India. The brief Sino-Indian war of 1962 when the two countries battled for control of the region, still has implications for India and China today, where they continue to dispute border lands.

As with many powerful nations, China has always been concerned about threats, or rival power bases, within its neighbourhood. This is similar to how the US has used the Monroe Doctrine to ensure its dominance over Latin America, and how Russia seeks to maintain its influence over former Soviet states.

Beijing views western criticism of its control of Tibet as interference in its sphere of influence.

Read more:
India and Pakistan tension escalates with suspension of historic water treaty

Another source of contention is that Beijing traditionally views boundaries such as the McMahon line defining the China-India border as lacking legitimacy, a border drawn up when China was at its weakest in the 19th century. Known in China as the “century of humiliation”, this was characterised by a series of unequal treaties, which saw the loss of territory to stronger European powers.

This continues to a source of political tensions in China’s border regions including Tibet. This is a controversial part of China’s historical memory and continues to influence its ongoing relationship with the west.

Demand for natural resources

Tibet’s importance to Beijing also comes from its vast water resources. Access to more water is seen as increasingly important for China’s wider push towards self-sufficiency which has become imperative in the face of climate change. This also provides China with a significant geopolitical tool.

For instance, the Mekong River rises in Tibet and flows through China and along the borders of Myanamar and Laos and onward into Thailand and Cambodia. It is the third longest river in Asia, and is crucial for many of the economies of south-east Asia. It is estimated to sustain 60 million people.

China’s attempts to control water supplies, particularly through the building of huge dams in Tibet, has added to regional tensions. Around 50% of the flow to the Mekong was cut off for part of 2021, after a Chinese mega dam was built. This caused a lot of resentment from other countries which depended on the water.

Moves by other nations to control access to regional water supplies in recent years show how water is now becoming a negotiating tool. India attempted to cut off Pakistan’s water supply in 2025 as part of the conflict between the two. Control of Tibet allows China to pursue a similar strategy, which grants Beijing leverage in its dealings with New Delhi, and other governments.

Another natural resource is also a vital part of China’s planning. Tibet’s significant lithium deposits are crucial for Chinese supply chains, particularly for their use in the electric vehicle industry. Beijing is attempting to reduce its reliance on western firms and supplies, in the face of the present trade tensions between the US and China, and Donald Trump’s tariffs on Chinese goods.

Tibet’s value to China is a reflection of wider changes in a world where water is increasingly playing an important role in geopolitics. With its valuable natural resources, China’s desire to control Tibet is not likely to decrease.

Tom Harper does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

– ref. China’s interest in the next Dalai Lama is also about control of Tibet’s water supply – https://theconversation.com/chinas-interest-in-the-next-dalai-lama-is-also-about-control-of-tibets-water-supply-255843

Source: The Conversation – UK – By Mark Horowitz, Visiting Clinical Research Fellow in Psychiatry, UCL

A new review of antidepressant withdrawal effects – written by academics, many of whom have close ties to drug manufacturers – risks underestimating the potential harms to long-term antidepressant users by focusing on short-term, industry-funded studies.

There is growing recognition that stopping antidepressants – especially after long-term use – can cause severe and sometimes debilitating withdrawal symptoms, and it is now acknowledged by the UK government as a public health issue.

One of the main reasons this issue took decades to recognise after the release of modern antidepressants onto the market is because medical guidelines, such as those produced by Nice (England’s National Institute for Health and Care Excellence), had for many years declared withdrawal effects to be “brief and mild”.

This description was based on studies run by drug companies, where people had only taken the medication for eight to 12 weeks. As a result, when patients later showed up with severe, long-lasting symptoms, many doctors didn’t take them seriously because these experiences contradicted what the guidelines led them to expect.

Our recent research helps explain this mismatch. We found a clear link between how long someone takes antidepressants and how likely they are to experience withdrawal symptoms – and how severe these symptoms are.

We surveyed NHS patients and found that people who had used antidepressants for more than two years were ten times more likely to have withdrawal effects, five times more likely for those effects to be severe, and 18 times more likely for them to be long lasting compared with those who had taken the drugs for six months or less.

For patients who used antidepressants for less than six months, withdrawal symptoms were mostly mild and brief. Three-quarters reported no or mild symptoms, most of which lasted less than four weeks.

Only one in four of these patients was unable to stop when they wanted to. However, for long-term users (more than two years), two-thirds reported moderate or severe withdrawal effects, with one-quarter reporting severe withdrawal effects. Almost one-third of long-term users reported symptoms that lasted for more than three months. Four-fifths of these patients were unable to stop their antidepressants despite trying.

About 2 million people on antidepressants in England have been taking them for over five years, according to a BBC investigation. And in the US at least 25 million people have taken antidepressants for more than five years. What happens to people in eight-to-12-week studies is a far cry from what happens to millions of people when they stop.

Studying what happens to people after just eight to 12 weeks on antidepressants is like testing car safety by crashing a vehicle into a wall at 5km/h – ignoring the fact that real drivers are out on the roads doing 60km/h.

History repeating itself?

Against this backdrop, a review has just been published in Jama Psychiatry. Several of the senior authors declare payments from drug companies. In what looks like history repeating itself, the review draws on short-term trials – many funded by the pharmaceutical industry – that were similar to those used to shape early treatment guidelines. The authors conclude that antidepressants do not cause significant withdrawal effects.

Their main analysis is based on eleven trials that compared withdrawal symptoms in people who had stopped antidepressants with those who had continued them or stopped taking a placebo. Six of these trials had people on antidepressants for eight weeks, four for 12 weeks and just one for 26 weeks.

They reported a slightly higher number of withdrawal symptoms in people who had stopped antidepressants, which they say does not constitute a “clinically significant” withdrawal syndrome. They also suggest the symptoms could be explained by the “nocebo effect” – where negative expectations cause people to feel worse.

In our view, the results are likely to greatly underestimate the risk of withdrawal for the millions of people on these drugs for years. The review found no relationship between the duration of use of antidepressants and withdrawal symptoms, but there were too few long-term studies to test this association properly.

The review probably underestimates, in our view, short-term withdrawal effects too by assuming that the fact that people experience withdrawal-like symptoms when stopping a placebo or continuing an antidepressant cancels out withdrawal effects from antidepressants. But this is not a valid assumption.

We know that antidepressant withdrawal effects overlap with side-effects and with everyday symptoms, but this does not mean they are the same thing. People stopping a placebo report symptoms such as dizziness and headache, because these are common occurrences. However, as was shown in another recent review, symptoms following discontinuation of a placebo tend to be milder than those experienced when stopping antidepressants, which can be intense enough to require emergency care.

So deducting the rate of symptoms after stopping a placebo or continuing an antidepressant from antidepressant withdrawal symptoms is likely to underestimate the true extent of withdrawal.

The review also doesn’t include several well-designed drug company studies that found high rates of withdrawal symptoms. For example, an American study found that more than 60% of people who stopped antidepressants (after eleven months) experienced withdrawal symptoms.

The authors suggest that depression after stopping antidepressants is probably a return of the original condition, not withdrawal symptoms, because similar rates of depression were seen in people who stopped taking a placebo. But this conclusion is based on limited and unreliable data (that is, relying on participants in studies to report such events without prompting, rather than assessing them systematically) from just five studies.

We hope uncritical reporting of a review based on the sort of short-term studies that led to under-recognition of withdrawal effects in the first place, does not disrupt the growing acceptance of the problem and slow efforts by the health system to help potentially millions of people who may be severely affected.

The authors and publisher of the new review have been approached for comment.

Mark Horowitz is the author of the Maudsley Deprescribing Guidelines which outlines how to safely stop antidepressants, benzodiazepines, gabapentinoids and z-drugs, for which he receives royalties. He is co-applicant on the RELEASE and RELEASE+ trials in Australia funded by the NHMRC and MRFF examining hyperbolic tapering of antidepressants. He is co-founder and consultant to Outro Health, a digital clinic which helps people to safely stop no longer needed antidepressants in the US. He is a member of the Critical Psychiatry Network, an informal group of psychiatrists.

Joanna Moncrieff was a co-applicant on a study of antidepressant discontinuation funded by the UK’s National Institute for Health Research. She is co-applicant on the RELEASE and RELEASE+ trials in Australia funded by the NHMRC and MRFF examining hyperbolic tapering of antidepressants. She receives modest royalties for books about psychiatric drugs. She is co-chair person of the Critical Psychiatry Network, an informal group of psychiatrists.

– ref. Antidepressant withdrawal: new review downplays symptoms but misses the mark for long-term use – https://theconversation.com/antidepressant-withdrawal-new-review-downplays-symptoms-but-misses-the-mark-for-long-term-use-260708