Winter Pioneer Research Magazine 2021

WINTER 2021 Great Ormond Street Hospital Children’s Charity

HENRY’S CHRISTMAS AT GOSH Meet Henry, who spent his first two Christmases in hospital

DIGITAL TECH AT WORK

Charity support helping develop technology at GOSH

THE POWER OF RESEARCH Building a better future for children at GOSH

CONTENTS 04 IN REVIEW Stories from around the hospital and charity.

06 ETHAN’S CHRISTMAS AT GOSH At just nine months old, Ethan spent his first-ever Christmas in hospital attached to a Ventricular Assist Device.

10 SUPERCHARGING DISCOVERIES Researchers who received National Call grants from GOSH Charity talk to Pioneer about what they’re hoping to achieve with their funding.

12 TREATING A NEW CONDITION Theophilos was treated at GOSH for PIMS-TS; the hospital was one of the first centres in the world to care for children with the condition.

16 COVER STORY

HENRY’S STORY: ONE STEP CLOSER TO HOME GOSH and charity support helped Henry get one step closer to home after he spent two Christmases in hospital.

As the Zayed Centre for Research into Rare Disease in Children celebrates its second anniversary, Pioneer looks at its achievements to date.

26 DIGITAL SCIENCE DRIVING PATIENT CARE Pioneer shines a light on how GOSH is developing digital technology to improve children’s hospital experience.

30 WHY I SUPPORT THE CHARITY: IVY RICHMOND In the run up to her 100th birthday last month, Ivy Richmond took on her very own Everest Challenge to raise money for GOSH Charity.

32 GOSH JOINS GLOBAL COLLABORATION ON GENOMICS GOSH and international colleagues share knowledge and expertise to pave the way to better treatments for children.

34 PARENT’S PERSPECTIVE Max started coming to GOSH at a few months old, after doctors discovered he was deaf. Mum Giulia shares his story.

18 THE TWO SIDES OF RESEARCH Pioneer explores how individualled programmes help improve the patient experience.

22 A CENTRE OF EXCELLENCE

All photographs included in this edition were either taken before the Coronavirus crisis, or were taken adhering to all government guidelines.

WELCOME Welcome to the Winter 2021 issue of Pioneer and another edition packed full of hospital news and inspiring stories of children and young people and the staff at Great Ormond Street Hospital (GOSH).

Throughout 2021, despite the many challenges we’ve all faced, Great Ormond Street Hospital Children’s Charity (GOSH Charity) has been able to continue helping GOSH transform the lives of seriously ill children.

Thanks to our generous supporters, we’ve continued to raise vital funds so the hospital can deliver life-changing care and discover new treatments and cures.

Now, in this issue, we’re highlighting more about the hospital’s ambitions, which ensure that bringing benefits to patient care, and putting the child first and always, remain at its very core.

From page 26 you’ll read about how GOSH will use developments in digital technology to improve on the hospital experience for children and their families, and how charity support will help. And, from page 22, you can find out how, as it marks its second anniversary, the Zayed Centre for Research into Rare Disease in Children – a partnership between GOSH, UCL Great Ormond Street Institute of Child Health and GOSH Charity – is propelling child health research into the future.

As we approach Christmas read more about how, during the festive period and throughout the year, your support can help GOSH get children one step closer to home and make the hospital feel like a home from home for those children who have to continue their treatment over the festive period. From page 16 you can read Henry’s story and from page 6 you can read Ethan’s story; both spent their first Christmas at GOSH and, through their stories, you can discover how your support helps.

I leave you now with this collection of personal and inspirational stories, which I hope will encourage you to continue supporting the incredible work that takes place both at GOSH and GOSH Charity.

Louise Parkes CEO Great Ormond Street Hospital Children’s Charity

On the front cover: Henry, now four, spent his first two Christmases at GOSH

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IN REVIEW

STORIES FROM AROUND THE HOSPITAL AND CHARITY

1 1

2 Above: Amelia-Rose loved the Play team when she was at GOSH

pinpoint where Riley’s seizures were coming from and safeguard him during the operation. The operation was a success and Riley hasn’t had a single seizure in two years.

Above: Vital operating equipment stopped Riley’s seizures

1 THANK YOU FOR SUPPORTING OUR VITAL EQUIPMENT APPEAL

Great Ormond Street Hospital Children’s Charity’s (GOSH Charity) Vital Equipment Appeal has raised an amazing £314,600, thanks to the generosity of incredible supporters like you.

Launched in May to fund the vital equipment needed for brain surgery, the appeal featured Great Ormond Street Hospital (GOSH) patient Riley, who had brain surgery at the hospital in 2019 to treat his epilepsy.

Riley was two when he started to have “the shakies”. His seizures got so bad that, one day, he had more than 100. When brain surgery was suggested, Riley’s parents were worried but were reassured by the state-of-the-art operating equipment that would be used, which would help

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The funds raised from the appeal will be used to upgrade the vital equipment that evaluates whether children like Riley are suitable for surgery, and which keeps them safe during operations. The new equipment will help the neurology team at GOSH make informed decisions, reassures patients and their families, reduces the risk of complications, and allows GOSH to treat more young patients.

This wouldn’t be possible without your support.

Thank you to our wonderful supporters who donated to this appeal.

2 SUMMER PIONEER APPEAL SUCCESS GOSH Charity would like to thank all its generous supporters who donated to our annual Summer Pioneer Appeal this July, which will fund both the important Play services at the hospital and life-changing research. You raised an incredible £278,000.

The summer edition of Pioneer featured a number of inspirational stories, including one about Sarah who, thanks to research into child health, received

gene therapy at the hospital. This groundbreaking clinical trial at GOSH is offering a cure to children born without an immune system. Following her gene therapy treatment, Sarah is doing well and can now live a normal life.

The appeal also highlighted the importance of the hospital’s Play team, who support children and families such as Amelia-Rose’s. At three months old, Amelia-Rose was diagnosed with an atrial septal defect: a hole in the heart. Within a year, she had three heart surgeries at GOSH. “The Play team was so important to us. Amelia always had a smile on her face and that was down to them,” Steph, AmeliaRose’s mum, says.

These incredible stories wouldn’t be possible without our fantastic supporters. Thank you once again from all of us.

3 GOSH CHARITY’S GREAT BIG LOTTERY The Great Big Lottery is a fun way to support the incredible work of hospital and be in with a chance to win great cash prizes. There are 12 guaranteed prizes to be won every week, with a top prize of £1,000! Visit lottery.gosh.org to play and you could be one of our lucky winners. Thank you if you have already signed up to the Great Big Lottery.

Winners will be contacted and can be found on lottery.gosh.org/winners.

to seriously ill children and their families. From everyone here – thank you!

You can now enter our annual New Year Megadraw Raffle! There is a top prize of £10,000 and we share how your support can help children treated at GOSH. To find out more information about this visit gosh. raffleentry.org.uk from the first week of January.

5 CHRISTMAS STOCKING APPEAL There’s still time to send a message of support on a Christmas stocking (enclosed with this magazine) to the seriously ill children, their families and staff at GOSH. Your heartfelt messages of sympathy and encouragement will bring the spirit of Christmas to children (like Ethan, pictured below) who need to stay in the hospital at Christmas with their families.

Your messages will help GOSH feel like a home from home. Please support our Christmas appeal: gosh.org/xmas or call 0330 0021514 to make a donation.

Thank you.

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4 NEW YEAR MEGADRAW RAFFLE 2022 Firstly, a huge thank you to everyone who took part in our Autumn Raffle this year. We had a fantastic response and raised more than £265,000. The money raised will help the charity continue to support GOSH as it provides extraordinary care and services

Above: Read Ethan’s story from page 6

1875

THIS TIME IN GOSH’S HISTORY

The first purpose-built clinical building at GOSH opened on 48-49 Great Ormond Street. It was designed by Edward Middleton Barry, son of Sir Charles Barry, co-architect of the Houses of Parliament.

It had four main wards, an operating theatre and an elaborate chapel that is now the only surviving part of the original building.

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ETHAN’S CHRISTMAS AT GOSH At just nine months old, Ethan spent his first-ever Christmas in hospital attached to a Ventricular Assist Device (VAD), or Berlin Heart, which kept him alive. Mum Roselelia shares their story with Pioneer.

When Ethan was diagnosed with dilated cardiomyopathy – a disease that affects the left side of the heart, making it harder for the muscle to pump blood around the body and which can cause heart failure – his dad Richard was still recovering from a heart transplant himself. He’d been diagnosed with a different heart problem from his son’s – arrhythmic right ventricular cardiomyopathy, which affects the right side of the heart – eight months earlier.

So the family already had a lot to cope with when Ethan first came to Great Ormond Street Hospital (GOSH). Mum Roselelia describes how the family felt when they first arrived.

“The nurses, consultants and the heart team were dealing with two very distraught parents, but the support we received throughout was second to none,” she says. “That is exactly what you want when you are there with your poorly child, knowing you can put your trust in someone to save them.

“All of the heart team and the nurses were amazing.

There were a few nurses on Bear Ward that we became very close with. Seeing them every day for a year, you create a bond. We would talk about everything and anything, including Ethan of course, but it was nice to know we made friends there too.”

CHRISTMAS AT GOSH On Christmas Eve 2019 Richard and Roselelia, and her two daughters Alanah and Maia, all stayed in family accommodation near GOSH, which is funded

by Great Ormond Street Hospital Children’s Charity (GOSH Charity). “We wanted to be there first thing in the morning to be with Ethan,” Roselelia says, “even if we had no idea what was happening! I made lots of buffet-style food and ordered loads of cupcakes to hand out to staff and other parents.

“Although we were spending Christmas at GOSH, eating buffet food and not a proper Christmas dinner, I still brought in a disco light and speaker and had all the kids dancing away in our bay! We were the loudest on Bear Ward. We even had some of the other children come and join us.

“We had the whole family around Ethan’s bedspace.

Even though it was a little cramped with us all in there, it didn’t dampen our spirits and we had an amazing day regardless.

“It’s about being together that mattered the most.

Just months before we didn’t even know if Ethan would be with us, so to be with him at Christmas made us feel so grateful.”

Roselelia also fondly remembers how much they all used to love reading the kind messages sent in by GOSH Charity supporters on the paper Christmas stockings.

“We would read all the messages while queuing for food, which was a well-needed break. It was so lovely to read the kind words and inspiration – they really keep you going when you’re in hospital at Christmas with your poorly little one. Thank you so much to all the charity’s supporters for taking the time to send messages in.”

VISITING THE HOSPITAL DURING LOCKDOWN In March 2020, when the first lockdown was announced, the one carer per patient rule was introduced at the hospital, which meant Roselelia had to spend months on her own in Ethan’s room while the rest of her family were at home.

“It was hard being on my own for four months during lockdown with Ethan and tiring as I was still working full time from his bedside. But I was determined to be there for him every day,” she says.

“The nurses were great in supporting us, but I felt constantly torn between not seeing my two daughters and leaving Ethan. The few times I did go home I felt guilty for not being in the hospital. I wouldn’t wish it on anyone; however, the nurses did an amazing job caring for him.”

GETTING THE TRANSPLANT CALL After months of waiting, Roselelia received the call in summer 2020 that Ethan would receive a transplant.

“Waiting for the call for a transplant was very hard,” she says. “We didn’t know if it would take place during the pandemic. Just before we started hearing about COVID-19 in the news, Ethan had been getting more tired. His oxygen levels were dropping, he needed blood transfusions and he was very poorly. He had an infection and was having more issues daily with his Berlin heart [a mechanical device used to support children in severe heart failure, either until recovery or until a heart transplant is possible] and clots.”

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Roselelia remembers how, one day in July last year, Ethan had a day where his head kept tilting. He was referred for a CT scan, which revealed he’d had mini strokes some months before. “We were told they didn’t know how these would impact him until he is at least two years old, as that’s when the brain is at its full development for his age,” she adds. “The areas affected in his brain could impact his memory, learning, behavioural and cause epilepsy, but we won’t know until we get to that stage and he is reviewed again. He is, however, showing no signs at the moment and developing well.

“Then the day we got the call to say a heart had been found I wept with relief. When he had the surgery, I held him in my arms and sang to him as he was given the anaesthetic and wheeled to theatre for six hours.”

The surgery was a success and Ethan was able to go home in time for Christmas in 2020.

BEING BACK HOME FOR CHRISTMAS “Having Ethan home was an amazing end to a difficult year,” Roselelia says. “I was looking forward to seeing him tuck into his first Christmas dinner

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with us all. Christmas has always been a huge celebration in our household as it’s also my mum’s birthday. And Christmas [2020] was perfect although, like everyone, we were in lockdown and unable to see family and friends. When the tree went up, I knew I’d have a battle on my hands with him trying to climb it but then I remembered this was the first time Ethan had seen a Christmas tree and really experienced Christmas Day. “On Christmas Day morning we all opened our presents together. Ethan had no idea what was happening, he was just so excited listening to his sisters squealing away, but at just 18 months old you don’t really know what is going on anyway. He was more excited about the wrapping paper than his presents! This year’s Christmas will be different as he will understand that little bit more about what’s going on.”

ETHAN NOW “Ethan has now been home for 15 months, the longest he has ever lived at home,” Roselelia explains. “He has definitely settled into his surroundings and family life. We celebrated his second birthday at home and he started nursery

in September, which isn’t something we even thought we could be discussing.

“He loves watching Mr Tumble and Mickey Mouse Club House – you get no response if they are on!

“He is learning to say a few words now and is really determined. We love his spirit – nothing holds him back. He loves playing with his sisters and with dinosaurs – shouting “roar” at them when he plays.

His favourite food is Weetabix, he is practically shouting at you to get it in his mouth as we get the box out the cupboard.

“Healthwise, Ethan is doing well, we’re very lucky he’s continuing to stay healthy. What GOSH did for us was amazing, we’re so thankful for everything and squeeze Ethan that little bit harder everyday – knowing the family of the organ donor would love to still be able to do the same.”

Ethan’s dad Richard adds: “We’re so grateful to the two families who said yes to organ donations and that Ethan’s recovery is going well. It’s lovely to be a proper family again under one roof and so nice to wake up each morning and hear Ethan chatting away to himself and watching him play with his sisters.”

“This Christmas we’re most looking forward to being home,” Roselelia adds. “We were in GOSH for more than a year and Ethan’s normal was to be surrounded by nurses in masks with mummy and daddy coming into to see him every day. Now, being together at home as a family is just amazing!”

CHARITY SUPPORT “Richard and I stayed in the family accommodation close to the hospital,” Roselelia adds. “I don’t think anyone can understand just how much of a help that was for us to stay a short 10-minute walk away from our son, as we live over an hour’s drive away from GOSH. We have had many late-night calls to get to the hospital quickly due to something happening with Ethan, and the stress of only having to get there in 10 minutes definitely alleviated our fears at the time. GOSH Charity funding the family accommodation near the hospital is amazing.”

You can make a donation to the GOSH Charity Christmas Appeal by visiting gosh.org/xmas or by calling 0330 002 1514.

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SUPERCHARGING DISCOVERIES GOSH Charity’s and Sparks’ National Call continues in its bid to support researchers across the UK as they investigate causes of rare diseases in children. Two researchers awarded grants tell Pioneer what they hope to achieve.

As part of its ambition to help unlock breakthroughs in child medicine, Great Ormond Street Hospital Children’s Charity (GOSH Charity) has awarded a £2.5 million investment into 11 pioneering child health research projects to researchers based as six institutions across the country. Funding from the GOSH Charity and Sparks National Call (the children’s medical research charity Sparks merged with GOSH Charity at the end of March 2021) is the UK’s largest charitable grant-making scheme of its kind dedicated to paediatric rare disease research.

Professor Siddharth Banka, University of Manchester Grant awarded to identify treatments for KMT2 chromatin disorders.

Q: What are chromatin disorders?

A: Chromatin disorders are a group of rare genetic conditions affecting brain development, which can result in neurodevelopmental disorders (NDD) such as intellectual disability and problems with other body systems.

There’s no set definition of what chromatin disorders are, but we think there are around 200 known 10 PIONEER

chromatin disorders and maybe one in 2,000 children will have one. We have little knowledge of how and why chromatin disorders cause NDD but recent findings suggest certain disorders may be treatable.

Q: What’s your plan for the grant?

A: Over the last few years we’ve been trying to work out the underlying mechanisms causing intellectual and neurological problems in a particular chromatin disorder called Kabuki syndrome type 1. So far there is no treatment for this condition.

The current grant proposal from GOSH Charity is an extension of our previous work in Kabuki syndrome type 1, which is caused by changes in a gene called KMT2D. We’ll study another chromatin disorder, Kleefstra syndrome type 2, caused by changes in the KMT2C gene. We suspect because these two genes are quite closely related, the similar approaches might help understand both the disorders.

We’ll conduct experiments to see how these genetic changes affect the development and function of brain cells. The final part of the research would be to identify potential therapies.

Q: What impact do you hope your research will make?

A: We hope our research to improve the understanding of these disorders leads to the identification of new treatments for them and increase the awareness of these diseases among clinicians, scientists and the general public. The lessons we learn for these conditions may have wider applications in several other disorders..

Q: Why is charity funding so important to your work?

A: Research funding for rare disorders affecting children is challenging to obtain. Funding from GOSH Charity, therefore, is crucial.

I’m enormously grateful to the charity’s supporters.

It’s their donations that will lead to real changes in people’s lives.

Dr Paula Alexandre, ICH Grant awarded to investigate the underlying causes of cerebellar developmental disorders.

Q: Why did you apply for the National Call?

A: I dedicated the last two decades to studying brain development and understanding the mechanisms that regulate neurogenesis, a process that generates new nerve cells (neurons) in the brain. My group and wide network of collaborators want to understand the underlying causes of cerebellar malformations. The cerebellum is a region at the back of the brain that plays a major role in movement, cognition, language and emotional processing. Problems in this region are generally associated with cognitive and speech impairment, epilepsy and movement disorders.

Q: Why is more research required into the underlying causes of human developmental brain disorders?

A: To understand the causes, one needs to understand human brain development, but most of the current knowledge in cerebellum development and malformations is based in animal studies. We’ve already shown that some critical developmental mechanisms aren’t shared between humans and animals. The developing human cerebellum contains specific zones that are expanded compared to other mammalian species. We want to know whether these zones are disrupted in diseases characterised by smaller cerebellums.

Q: What will the grant allow you to do?

A: Financing will allow us to establish the first human cellular model at ICH to study cerebellum development, investigate the cellular and molecular causes of the cerebellar hypoplasia, a developmental malformation characterised by a reduced cerebellum volume, and test potential therapies. Initially, we’re planning to focus on Down’s syndrome and Non-Ketotic Hyperglycinemia (NKH), two conditions that can present cerebellum hypoplasia.

Q: Why is this grant essential to your work?

A: New funds are crucial to develop a new line of research in the lab, supported by an interdisciplinary group of local and international researchers, world leaders in their fields.

This project involves cerebellum development experts in the US, Professor Kathleen Millen and Dr Parthiv Haldipur, and ICH researchers Professor Nick Green, an authority in NKH, and Professor Patrizia Ferretti and Professor Rick Livesey, specialists in neuro stem cells.

GOSH Charity is one of the few organisations sponsoring child health research. Supporting child health research is an investment into a better future for many children and their families.

FIND OUT WHERE THE GRANTS HAVE BEEN AWARDED 1 University of Warwick • Developing a clinical checklist to ensure causes of poor behavioural outcomes in children with intellectual disability are routinely considered.

CL Great Ormond Street Institute of 2 U Child Health • See this page.

• Generating human models of acrodysostosis – a group of rare genetic disorders causing abnormal skeletal growth and can also affect neural development – for testing mechanisms and pharmacological intervention.

• Leveraging transcriptomics to improve the diagnostic rate and understanding of neurometabolic disorders.

3 University College London • Targeting amino acid metabolism as a novel treatment avenue for DiamondBlackfan anaemia, an inherited condition caused by errors in genes coding for ribosomal proteins.

• Dissecting the role of mechanical lung compression in congenital diaphragmatic hernia on a single cell level.

4 University of Southampton • Developing and validating a paediatric pain assessment tool for children with cancer and life-limiting conditions.

5 University of Cambridge • Identification of pathways that protect against beta-propeller protein-associated neurodegeneration.

6 University of Manchester • See page 10.

7 University of Oxford • The treatment of Dravet syndrome.

• Reversing zeta-globin transcriptional silencing: towards embryonic globin induction in patients with severe alphathalassemia.

Two grants were part-funded by condition-specific partner charities (Acrodysostosis Support & Research and Dravet Syndrome UK) to help co-fund research into these diseases.

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TREATING A NEW CONDITION GOSH was one of the first centres in the world to care for children with paediatric multisystem inflammatory syndrome (PIMSTS), a rare syndrome associated with COVID-19. The hospital treated 11-year-old Theophilos and mum Hannah shares his story with Pioneer.

Theophilos with his mum and sisters

In early May last year, my son Theophilos started vomiting. By the next day, he couldn’t eat or drink. I thought it was a stomach bug, so I called NHS 111.

Theophilos was assessed over the phone, and it was agreed a bug was the likely cause. But, by this point, Theophilos had a temperature and, a few days later, he was still struggling to eat and drink. He had now developed bloodshot eyes, which really worried me – so I called an ambulance, although he wasn’t admitted to hospital at this point.

Just a couple of days later, however, he could no longer stand by himself or walk. I called an ambulance again and Theophilos was rushed to our local hospital in Southend, Essex.

It was the scariest moment of my life. He had suspected sepsis and was given IV treatment and his hands were so cold but his legs and other places in his body were so hot. His temperature wouldn’t come down and the water was no longer circulating in his body.

It was confirmed he had sepsis and systemic inflammatory response syndrome. I was then asked if there was anyone I could call, because I should have people around me. When I heard those words, I was so shocked I didn’t know what to say. Tears were coming out of my eyes, but nothing was coming out of my mouth. I prayed.

Theophilos was moved to the paediatric intensive care unit (PICU) and I had to put on protective clothing to join him. The staff at our local hospital did a fantastic job and were on the phone constantly to other centres to try and establish what might be wrong with him. Around two hours later, specialists arrived from Great Ormond Street Hospital (GOSH) and he was transferred to the hospital.

“A specialist nurse was waiting for us on arrival at GOSH. She was so reassuring and completely focused on what she needed to do.”

ARRIVING AT GOSH When Theophilos arrived at GOSH, his blood was clotting, he had an acute kidney injury and an inflamed stomach. In addition, he was hallucinating and didn’t know where he was. A specialist nurse was waiting for us on arrival. She was so reassuring and completely focused on what she needed to do.

While on GOSH’s PICU, the main thing was to try and stabilise his organs, especially his kidney and, because he also had irregularity in his blood formation, that had to be treated as well.

What was strange was that he had many COVID-19 tests, but they came back negative. GOSH doctors explained that even though COVID-19 was not in his system, this didn’t mean he hadn’t had an encounter at some point. Later, when he had an antibody test, it was confirmed he had many antibodies in his system and this might have been part of the problem. His body was just fighting back.

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Theophilos is now doing well and passed his 11+ exam last year

reassured me she was going to look after Theophilos and would call me if anything happened. The accommodation was just a two-minute walk from GOSH and funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity). It was a very difficult time; because Theophilos was so ill I couldn’t go home to see my two teenage daughters and had to make plans for them both.

That first night, I couldn’t sleep, but was grateful to know I wasn’t too far from my son. By 6am, I was back at the hospital and the same nurse was still there to greet me.

I don’t know what she must have gone through during the night to stabilise him, but what I do know is the first few hours were critical to his recovery and she did a fantastic job. I’m forever grateful for that.

FROM PICU TO HEDGEHOG WARD TO HOME After spending three days on GOSH’s PICU, Theophilos moved to Hedgehog Ward where he stayed for a further six days. During this time, he was seen by numerous different clinical teams, but also by the Play team, who gave him books and games to play with if he was feeling up to it. As he couldn’t walk, he had physiotherapy and, due to his heart rate being low, he was also monitored by cardiologists.

Nine days later, he was able to go home.

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Theophilos’ next appointment was six months later, in December 2020, where doctors checked his heartbeat and his overall health. All was fine and during this visit he had a test that revealed he still had a lot of antibodies in his system seven months later. We were asked if we would be happy for his blood to be used for research purposes because of this. I was happy to consent because if the research can help save other children, then it’s absolutely worth it.

Then, a year after Theophilos’s first visit to GOSH, he had a one-year review, having an ECG (electrocardiogram) to check his heart. Thankfully, this was all fine too.

GRATEFUL TO GOSH Today, Theophilos is doing well. He even sat his 11+ exam in November the day before his birthday and, despite everything he has been through, he passed.

I’m forever grateful to every single person who was involved in Theophilos’ treatment and monitored him 24/7.

It’s a fantastic service at GOSH and it’s clear that charity funding for the hospital makes such a difference. I don’t know anyone who has experienced an intensive care unit, but I know you would want to receive the same care that Theophilos and I received.

Due to the nature of this new condition, and the range of organs affected, the care of these children could only be delivered through a multidisciplinary approach.

Good, quick and effective communication between several teams representing various medical specialties was key to our success.

GOSH PERSPECTIVE While at GOSH, Theophilos was under the care of multiple teams.

GOSH Consultant Cardiologist Dr Filip Kucera talks about PIMS-TS and Theophilos’ case.

Unlike in adults, COVID-19 is usually mild in children. It only rarely causes severe symptoms requiring hospitalisation.

However, a very small proportion of paediatric patients with COVID-19 develop an overexaggerated systemic inflammatory response. This occurs typically two to four weeks after the infection with the virus.

PIMS-TS was first described in April 2020 after UK doctors noticed a cluster of unusual hospital admissions of seriously ill children. They all showed signs of extreme inflammation associated, in most severe cases, with single- or multi- organ failure.

Many of them were critically unwell.

Although some of the symptoms observed in PIMSTS shared similarities with Kawasaki disease or toxic shock syndrome – two uncommon conditions – this disease was a journey into the unknown.

“Due to the nature of this new condition [PIMS-TS], and the range of organs affected, the care of these children could only be delivered through a multidisciplinary approach.”

This list of specialties would be very long, but would include paediatric intensive care, infectious diseases, rheumatology, cardiology, haematology, neurology, physiotherapy and many others. In a way, COVID-19 has brought us closer as teams than anyone could have expected.

Approximately 40% of patients admitted with PIMS-TS had cardiac issues ranging from minor ECG abnormalities and mild dilatation of the coronary arteries to life-threatening heart failure.

Many patients, such as Theophilos, initially required aggressive treatment to support their heart so their blood pressure did not drop too low, leading to insufficient blood flow to vital organs.

Fortunately, the clinical course of PIMS-TS is different from what we saw in the pre-COVID era in patients with inflammation of the heart muscle (myocarditis).

In myocarditis, complete recovery of cardiac function is non-universal and, if it happens, it usually takes a long time.

In PIMS-TS, in the majority of cases, the pumping function of the heart is typically normalised within a couple of days of adequate treatment. The main factor leading to recovery of cardiac function is reduced inflammation.

One of the other major concerns in PIMS-TS is abnormal blood clotting. From that point of view, blood thinning therapy was initiated in most patients. Luckily, Theophilos did not develop any thrombotic complications and, a few weeks after discharge, we were able to stop his preventive blood thinning therapy.

He has remained under our care in the multidisciplinary PIMS-TS clinic, which involves all relevant medical specialities.

GOSH was one of the very first centres in the world to look after children with PIMS-TS. Due to an early and extensive exposure to this disease, we played a fundamental role in sharing our experience with other centres not only in the UK, but across the globe.

Clinical research was our other strength.

I wish Theophilos all the best for the future.

Reassuringly, our experience has shown that patients with PIMS-TS are unlikely to encounter longterm cardiac complications.

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Henry arrived at Great Ormond Street Hospital (GOSH) on 23 December 2017 and had surgery on his windpipe and his pulmonary artery reimplanted. Shevonne recalls how she, and her husband Ben, were given hope and strength at a difficult time by the teams at GOSH. “We were so worried and concerned for what lay ahead,” Shevonne says. “Then when we came in to see Henry early in the morning on Christmas Day, he had a stack of presents at the end of his bed. He was ventilated and sedated but Santa still delivered his toys to him. Having the gifts gave us something to talk to Henry about while he lay there fighting for his life. It gave us purpose and we knew he wasn’t missing out on Christmas.”

ONE STEP CLOSER TO HOME Four-year-old Henry spent his first two Christmases at GOSH. Now, as the animated star of GOSH Charity’s Christmas Appeal, his mum Shevonne tells Pioneer how the hospital, and support from the charity, helped get Henry one step closer to home.

Henry was born at term but was transferred to a special care baby unit in Hull immediately, due to respiratory concerns and suspected gastric issues.

He had a colostomy and two holes in his heart were discovered. After a few days his breathing became irregular, followed by a diagnosis of long segmented tracheal stenosis and left pulmonary artery sling.

Henry’s windpipe (trachea) was 1.5mm wide; it should have been 6-8mm. His left pulmonary artery was also passing between the trachea and oesophagus, wrapping around his windpipe, and his trachea was made of complete cartilage rings, which wouldn’t have grown with him.

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Following his surgery, Henry required 24 hours of Continuous Positive Airway Pressure (CPAP) ventilation for three months. Then, doctors attempted to wean him from constant ventilation at his regional hospital.

During this time, he had a respiratory arrest. Leeds stabilised him on life support then he was transferred back to GOSH’s Cardiac Intensive Care Unit. With its specialist knowledge around his condition the team was able to move him from life support back to CPAP. Henry then went through a period of transitioning between life support and CPAP. “It was a worrying time and there were many occasions when we almost lost him,” Shevonne says. “In 2018 Henry was given airway stents [devices to keep the trachea open] as well as other gastric surgery and the formation of a gastrostomy [a feeding device directly connected to the stomach] as he couldn’t eat or drink orally while on CPAP. He was then given a

tracheostomy [a breathing tube fed through a hole in the throat] and ventilator to secure his airway and prevent repeat intubations.”

Once Henry came out of intensive care, he transferred to Kangaroo Ward, where they spent his second Christmas. “I went to town decorating his bay; it was full of twinkly lights, cards and balloons,” Shevonne says.

“We also stayed in family accommodation - funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity) - for two weeks over Christmas, which meant my husband and I could live as a family with Henry for the first time since he was born. It also allowed for some of our family and friends to visit over the Christmas period. We had a wonderful Christmas in the flat and will forever be grateful for the time there and the confidence it gave us to be able to care for our little Henry bear.”

Henry came into the hospital twice a day over the Christmas period for physio. Shevonne remembers how GOSH staff made the wards as festive and special as possible. “They dressed up on Christmas Day and there were decorations wherever you turned. It was heart-warming to know donations had been made to go towards giving seriously ill children the Christmas they deserve.”

After his second Christmas at GOSH, the long-term ventilation team helped prepare the family for Henry’s transition home.

“We were responsible for all of his care, medications, ventilation and equipment. It was nerve-wracking, but also reassuring to know if we could do this across the road from the hospital, we could do this at home.”

Henry now “Henry is a kind, happy and gentle child. He loves books, playing outdoors with water, riding his bike and scooter and going to his grandad’s farm to ride on the tractor with him. He loves acting out parts of his favourite stories or parts of a movie he likes. He’s a real character, often making us laugh and is a very good big brother to his baby brother George.

“Henry still requires 24-hour ventilation via his tracheostomy, however he has a voice now and can talk, which we never knew if he’d be able to do, due to him having a paralysed vocal cord post-surgery at five weeks old. Henry used Makaton sign language to communicate when he had no voice and now uses Makaton to support his speech. His voice is getting stronger and he is making himself understood.”

Henry now has six monthly reviews at GOSH as well as regular contact to manage his respiratory care at home and make any adjustments to ventilation or treatments.

“Everyone at GOSH is so supportive and we trust in their decision making about Henry’s care as they have got him this far. Everything from GOSH has been excellent.”

CHRISTMAS APPEAL Every child should have the chance to be at home with their families on Christmas Day. Dedicated teams at GOSH work around the clock to find cures and treatments to ensure seriously ill children have the best chance of getting home to their families.

By supporting GOSH Charity this Christmas you’ll be helping fund vital resources that GOSH needs to get seriously ill children one step closer to home. Resources such as state-of-the-art medical technology; pioneering research programmes into treatments and cures for rare conditions; patient and family support services; and new child-focused environments that help children feel safe and calm.

This festive season, look out for GOSH Charity’s Christmas Appeal. It will be spearheaded by an animation that highlights how donations can help bring children, like Henry, who stars in animated form (pictured above), one step closer to home.

Thank you for supporting GOSH Charity this Christmas. Visit gosh.org/xmas or call 0330 0021514 to make a donation.

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THE TWO SIDES OF RESEARCH

GOSH is dedicated to giving children in its care the best possible outcomes. Pioneer explores how its individual-led research programmes are helping improve the patient experience.

Pioneering research, leading to new treatments and cures for some of the most complex childhood conditions, has been at the epicentre of Great Ormond Street Hospital’s (GOSH) work throughout its almost 170-year history.

It’s achieved breakthrough after breakthrough, alongside its research partner UCL Great Ormond Street Institute of Child Health (ICH) and others.

And funding these research programmes remains a priority for Great Ormond Street Hospital Children’s Charity (GOSH Charity).

Equally key, however, is the hospital’s dedication to an all-round holistic approach to the care of its patients – and that means truly understanding what impact illness and disability has on children and young people.

This is where individual-led research programmes step in, enriching the world-class clinical care the hospital offers.

INTRODUCING ORCHID Leading the way in individual-led research programmes at GOSH is its Centre for Outcomes and Experience Research in Children’s Health, Illness and Disability (ORCHID). A dedicated research unit at the hospital comprising experienced senior researchers from nursing, allied health and the social sciences, the centre’s main work is to conduct child and family focused research. It does this through a range of quantitative and qualitative research studies, all working towards delivering better patient experiences.

NIHR GOSH Biomedical Research Centre (NIHR GOSH BRC) Clinical Academic Programme Lead based in ORCHID, Dr Polly Livermore, is a dedicated advocate for nursing and allied health professional clinical research. Having worked at GOSH since 1997 – as a rheumatology nurse, research nurse and matron – she studied for her National Institute for Health Research (NIHR) funded PhD, supported by ORCHID, researching psychological support for children with a rare, rheumatological condition called juvenile dermatomyositis (JDM). Dr Livermore now splits her matron role with her role at ORCHID, supporting people in the Trust who might have research questions in their specialty areas and directing PIONEER 19

LUKE’S STORY ORCHID Senior Research Fellow and GOSH Speech and Language Therapist Dr Debbie Sell worked with Luke, who was diagnosed with Apert syndrome, on speech therapy at GOSH. Looking to find out if parent-led speech therapy for children with cleft palates would be a positive step for patients, Dr Sell invited Luke’s family to participate in a research study, that has since led to the launch of www. speechathome.org. Luke’s mum Jacintha tells Pioneer why she feels this type of research is so valuable.

“Our journey at GOSH began when Luke was just three days old. When I was pregnant with him, we knew there’d be complications – the sutures in his skull were joined and we knew his facial bones would grow more slowly. But just after he was born he stopped breathing and was rushed to the intensive care unit at GOSH. He was on a ventilator for around two months and had an operation to correct his aorta at 10 days old; he was extremely poorly. Since then, because of his condition, he’s had regular appointments with the GOSH cranio-facial team, which includes audiology, ophthalmology and orthotics.

“As he was born with a cleft palate, which affected his speech, he had a lot of speech therapy at GOSH and that’s where we met Dr Sell, who asked if would be interested in taking part in a research study to see if parents could learn how to help their children with speech therapy at home.”

As part of the research study, Jacintha undertook training under the supervision of a therapist and then worked with Luke on what she’d learnt; both Jacintha and Luke found it to be a positive experience.

Jacintha adds: “I’d recommend other families take part in research studies if they’re available, it was so helpful to us and is great for the overall patient experience.”

Luke now Luke is now 11 and loves sport, especially football – Harry Kane is his favourite player – and he really loves maths! He’s just started secondary school, which was really emotional for us; he’s done so well and doesn’t need a one-to-one helper; and I believe that’s because he received such excellent care at GOSH. He’s fiercely independent and using the skills he’s been given through his therapy at the hospital and what we’ve able to do at home, following the research study. Luke is a product of excellent care, thanks to the multi-disciplinary teams working together at GOSH.”

them how to investigate their questions. She also leads on the BRC’s funded internship scheme, which runs annually and provides weekly teaching sessions to help future clinical research leaders apply for external funding to be able to answer their research questions.

families about how it can help improve their patient experience. It’s been proven that a research-minded hospital does better with outcomes, and this is also high on the agenda for the Care Quality Commission [the independent regulator of all health and social care services in England].”

“Nursing- and allied health professional-led research (such as physiotherapists, dieticians and many more professional groups) is just as important as medically led research – especially as GOSH is a research hospital,” Dr Livermore says. “We should be encouraging and supporting all staff to question the evidence out there and think about how to improve practice. If all of GOSH is thinking, challenging and questioning, if we can encourage everyone to get involved and be aware of what research is happening out there, we can talk more effectively to

PATIENT INVOLVEMENT IN CARE

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Research undertaken by researchers at ORCHID explore the experiences of the children and young people at GOSH and uses different research methodologies for different ages. “For example, in my PhD research I used a methodology called phenomenology, which gives children the opportunity to share how they really feel about living with their condition (in this case JDM). I gave them cardboard body maps to draw and write

Dr Polly Livermore

on, explaining how they experienced their illness,” she says. “For example, one girl drew some scales because she’d lost weight and drew a chair because she couldn’t stand. The children were so pleased that someone had asked them what it was like to live with their condition, they wanted to share their stories and improve things for other future patients.

“The children’s stories were always heartfelt and it’s emotional hearing about their journeys and experience. And then it’s about how we present those experiences back to clinicians. For example, I began to create poems from their interviews – they are all using the children’s own words and represented like this they are very powerful. I presented these at a conference and I was approached by a doctor who said he only used to ask the parents how the child was, often because the children would look at the floor and not want to join in during clinic appointments. Now though, he would make more of an effort to talk to the children and really find out how they are and what he can do to help them.”

Various research methods are used by researchers across ORCHID. Dr Livermore highlights the work of Professor Faith Gibson, ORCHID’s lead and GOSH Director of Research for Nursing and Allied Health at GOSH and Professor of Child Health and Cancer Care at Surrey University, who has used many innovative and creative ways to conduct research and share research findings. These include using puppets to communicate with four- to five-year olds undergoing cancer treatment and a collaborative theatre performance to share the findings from a research study looking at cancer care. Senior ORCHID Research Fellow and Consultant Nurse for Learning Disabilities Dr Kate Oulton has worked tirelessly conducting research with children with learning disabilities. In one study, for example, children decorated money boxes based on a key like and dislike (e.g. favourite/ least favourite colour or football club) to represent ‘good’ and ‘bad’ and then selected hospital flashcards to put into each as a way of sharing their views and experiences.

“One of the great things about ORCHID is it’s so collaborative and works hard to bring everyone across GOSH together,” Dr Livermore adds. “The big funded clinical studies are brilliant, but there’s set criteria about who can go into these. Nurses and allied health professionals, who are working on the wards, have their own questions that arise out of their day-to-day work, often about better ways of delivering care or ideas about how to improve practice. Asking appropriate questions will help us all improve the care we give. We also work closely with the GOSH Learning Academy [part-funded by GOSH Charity] to achieve this and it’s about giving everyone in the Trust the opportunity to undertake research in their areas.”

CHARITY FUNDING MAKING IT POSSIBLE Research opportunities through ORCHID are also thanks, in part, to GOSH Charity funding. GOSH nurse Pippa Sipanoun is currently undertaking a research study, supported by the charity, looking into patients’ experiences of GOSH’s electronic patient record Epic, which itself is charity funded. And Dr Livermore herself has received a scholarship award funded through the charity to take her research into the next stages.

“We want to say a huge thank you to GOSH Charity. It means the world to be able to undertake research to improve experiences for children and young people as they go through a worrying time, and we’re so grateful to all the charity’s supporters.”

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A CENTRE OF EXCELLENCE As GOSH celebrates the second anniversary of the Zayed Centre for Research into Rare Disease in Children, Pioneer explores the remarkable facility and how it’s shaping the future of research into child health.

Two years ago, a facility opened at Great Ormond Street Hospital (GOSH) that would herald a new era in translational research at the hospital.

The Zayed Centre for Research into Rare Disease in Children was designed to offer a unique crossplatform approach to paediatric research and care in a state-of-the-art facility. It’s here that pioneering research and clinical care come together under

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one roof, helping drive forward new treatments and cures for seriously ill children in the UK and across the globe. A partnership between GOSH, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital Children’s Charity (GOSH Charity), it was made possible thanks to a transformative £60 million gift from Her Highness Sheika Fatima bint Mubarak, wife of the late Sheikh Zayed bin Sultan Al Nahyan, Founder of the United Arab Emirates. Major contributions were also made

by Research England, The Wolfson Foundation, John Connolly & Odile Griffith and the Mead Family Foundation.

Despite the COVID-19 pandemic, the Zayed Centre for Research continued to be at the forefront of research. In fact, its people, skills and world-class facilities were chosen to focus on research activity to understand the virus.

Take a look at what’s inside…

Laboratories

GMP suite

Falcon outpatients

PLAYING A PIVOTAL ROLE IN THE PANDEMIC: The Zayed Centre for Research houses a specialist Good Manufacturing Practice (GMP) facility – the largest single academic manufacturing unit for gene and cell therapies in the UK and one of the largest in the world. It was chosen to play a key role in the world’s first COVID-19 human challenge study, manufacturing the virus used in the trial.

Researchers also ‘sequenced’ more than 15,500 COVID-19 genomes, to help scientists learn about the gradual changes in the virus over time showing how it spreads through different parts of the population.

Entrance to Falcon outpatients

GMP suite

3D printed hearts

400 RESEARCHERS AND CLINICIANS ARE BASED AT THE ZAYED CENTRE FOR RESEARCH THERE HAVE BEEN MORE THAN 95,000 PATIENT VISITS SINCE IT OPENED PIONEER 23

THE PIONEER INTERVIEWS Dr Mark Kristiansen, Head of UCL Genomics, and Professor Claire Booth, Mahboubian Professor of Gene Therapy at UCL Great Ormond Institute of Child Health (ICH), both based at the Zayed Centre for Research, tell Pioneer how the facility has positively impacted their work.

What role does genomics research [the study of people’s genes – without which there would be no understanding of genetic conditions] have at the Zayed Centre for Research?

The genomics facility comprises a number of dedicated areas, from gene sequencing and pathogen [virus/ bacteria] genomics to quality control and education.

We can support and process more than 1,500 projects per year from many scientific and medical disciplines. The Zayed Centre for Research has allowed us to accommodate a large number of automated technologies, with the dynamic and experienced team at UCL Genomics at the heart of it all! We’ve also doubled to 10 specialists, plus have staff supporting us to run COVID-19-related projects and quality control.

What other benefits does working here bring?

Our new dedicated laboratories mean we are now better able to collaborate with our colleagues, including our clinical partners. For the first time, all of our genomics equipment and, importantly, the entire facility team, are housed together in the same

Dr Mark Kristiansen

dedicated space, strengthening and increasing the overall capacity of the genomic sequencing stream.

Has the Zayed Centre for Research allowed your team to develop more highlyspecialised techniques?

We’ve been able to refine some of our existing streams, either through research and development and/or increased automation. One example is our methylation* clinic, now a global resource, offering a fast turnaround service provision model. Dedicated premises and a strong infrastructure allow us to offer what was a national, once-weekly service provision model multiple times per week internationally. We have more than 200 clinical and research partners both nationally and internationally accessing this popular stream, as well as many new collaborations.

How does the Zayed Centre for Research’s design allow for more effective working?

I was involved in the genomics lab design from the outset, futureproofing for expected increase in demand for genomics service provision. The lab’s design ensured we could maintain social distancing during the pandemic. The team was able to work flexibly and safely and we were able to incorporate a COVID-19 sequencing stream within just one week, something that would have been impossible before our move here.

How will the Zayed Centre for Research help more children in the future?

In the era of personalised medicine, teams like UCL Genomics must remain at the cutting-edge and be internationally accessible to continue to support scientific advances. Having experienced specialists in a well-equipped facility ensures we continue to support the future of genomics at a research and clinical level, benefitting children with rare conditions globally.

*Methylation can allow scientists to identify important biomarkers or predictors of disease/disease progression

come through, making them feel that they are at the heart of research. And it also allows the researchers to see the patients coming in for appointments, meaning they’re much closer to seeing what their work means to children and their families.

Mahboubian Professor Claire Booth

As co-lead author of the research study into a new type of gene therapy, which can cure severe combined immunodeficiency due to adenosine deaminase deficiency (ADASCID), what role did the Zayed Centre for Research play?

Studies of gene therapy to treat ADA-SCID [a rare, lifethreatening disease, where children have no immune system] have been running for 20 years. These studies were developed by GOSH Professors Adrian Thrasher and Bobby Gaspar, and began life at the ICH. Now that we’re based in the Zayed Centre for Research, and using its fantastic Good Manufacturing Practice (GMP) facilities, this means we’ve been able to increase the number of products we create to help patients.

What are the main benefits of being based here?

Early last year (pre-pandemic) we transferred the manufacture of the products for ADA-SCID as well as most of the team, including research nurses and project managers, to the Zayed Centre for Research.

And although we only had a few months of everyone being in the same place before the pandemic, we had a taste of how the infrastructure here will improve things in the future.

The fact you have the co-localisation of all the teams that are required to successfully deliver these clinical trials and therapies is helping to streamline processes.

Great Ormond Street Hospital (GOSH) has a fantastic history of translational research so we already had a strong base to build from, but the Zayed Centre for Research allows for the research scientists, who are developing the therapies, to be in the same building as the clinical team delivering the therapies. That really makes a difference because every team sees what the others are doing.

Most importantly, the outpatient facility here has a stunning walkway for children and their families to

What does the Zayed Centre for Research enable researchers to do now that they couldn’t do before?

When working in rare disease research it’s imperative we have robust networks across the world for clinical trials. For example, the ADA-SCID trial was in collaboration with University of California, Los Angeles, we have a trial running with Boston’s Children’s Hospital, as well as research partners in Madrid, Spain and Stanford University, California.

We now have a stronger network than ever with other centres around the world developing gene therapy and it’s important we stay leaders in the field. The Zayed Centre for Research has certainly made this easier.

For example, we’re able to develop new techniques for monitoring gene therapy patients. That’s an area we’re likely to expand on and something I would expect other centres would want to collaborate with us on.

What’s it like to work at the Zayed Centre for Research?

It’s inspiring – I come out of my office and see the research and clinical teams located on the same floor; there’s open-plan seating areas available that are conducive to teams sitting together [social distancing], where they can share ideas and plan patient care.

Being at the Zayed Centre for Research has certainly created strong team cohesion.

How important is charity funding when it comes to supporting new infrastructure at GOSH? The GMP facility at the Zayed Centre for Research means we can make more products and treat more children, and this couldn’t have happened without charitable investment.

We now have a really strong foundation to build on for future research and want to focus on how we can better monitor the safety and efficacy of therapies and try to make those as widely relevant and accessible as possible.

We’re now developing technologies that are available for a much wider range of diseases and we still need the funding and support to be able to do that.

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DIGITAL SCIENCE DRIVING PATIENT CARE Pioneer discovers how GOSH will use digital technology developments to improve on the hospital experience for children and their families and how charity support helps.

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Artificial intelligence (AI), virtual reality (VR), robotics – as healthcare becomes increasingly digital, how can these advances in technology help improve patient care and experiences at Great Ormond Street Hospital (GOSH)?

It’s a question the hospital continuously asks itself; and just one organisation supporting it to look for the answer is Great Ormond Street Hospital Children’s Charity (GOSH Charity). From the launch of Epic, GOSH’s patient record system in 2017 – which led to GOSH being recognised as one of the UK’s most digitally advanced hospitals – to supporting the Data for Research, Informatics and Virtual Environments Unit (DRIVE), GOSH Charity has consistently championed and funded digital transformation at GOSH. Bringing together leading industry experts in technology, AI and digital innovation, DRIVE is a unique partnership between GOSH and UCL Great Ormond Street Institute of Child Health (ICH). At its heart are teams who manage the Digital Research Environment (DRE) – which provides the technological infrastructure to facilitate research undertaken at GOSH – and the GOSH Charity funded Clinical Informatics Research Programme (CIRP), which works closely with ICH.

DRIVE’S DIGITAL OUTLOOK DRIVE’s Director, Chief Research Information Officer and Professor of Pathology at ICH Neil Sebire, highlights the short- and long-term digital areas the unit will be focusing on, designed to ultimately enhance children’s experience of GOSH. “The short-term key focus is around clinical decision support,” he explains. “This is where we look at where we can have digital tools that will help a doctor or nurse make a better decision on how to manage an individual patient. At its simplest, this could be an alert on an electronic patient record system saying this patient should or shouldn’t have a particular medication. But we’re also working on machine

“Ultimately, we want everything we do to be judged on whether there’s patient benefit.” learning and AI to look at data we have on previous patients to help make better management decisions on future patients.”

The second area of focus, which DRIVE has begun work on, is in operational decision support. This is asking whether the rich data GOSH has available can be used to help the hospital run more efficiently, for example in better scheduling to reduce cancellations. “Then a longer-term area of focus is around technology for patient monitoring,” Professor Sebire adds. “This is where we use digital innovations to help patients manage their conditions better, perhaps with an app attached to a Fitbit or something similar, to keep them healthy at home. This is a real part of DRIVE’s ambition, but it needs a different type of infrastructure, software developers, coders etc. While we don’t have the resource for this right now, the aspiration is for this area to grow.”

HOW CHARITY SUPPORT HELPS It’s within DRIVE’s Clinical Informatics Research Programme that we can see just how GOSH Charity support is helping. The CIRP is specifically designed to support research in clinical informatics, a new and evolving area of medicine, and it’s through this programme that charity funded grants are awarded.

“This programme is about bringing clinical and nonclinical people together,” Professor Sebire explains.

“It’s where computer science students interested in healthcare come to work with clinical supervisors at GOSH and computer science supervisors in DRIVE to develop and test early prototypes. It’s not about developing an algorithm that would work on a super computer, but developing something that can be used in real-world clinical care.”

Professor Neil Sabire

There are some exciting projects currently taking place at CIRP that are funded, or part-funded, by

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“The VR software enabled us to put goggles on, use two hand controllers and feel as if we were moving through Joe’s heart, which was absolutely amazing.” when Joe was 15 also indicated this. He then needed further surgery to correct and replace a section of his aorta.

TECHNOLOGY IN ACTION Joe, now 18, was the first-ever patient at GOSH to make use of virtual reality (VR) technology to examine the site of one of his procedures.* At just eight years old, scans taken at his local hospital revealed Joe had a leaking valve in his heart. He was referred to GOSH for surgery to repair his mitral valve.

“The valve wasn’t shutting properly and was letting blood flow back into upper chamber of the heart,” Joe’s mum Melanie says. “His heart was having to work harder than it should have been, which could leave him tired. The surgeon was able to tighten up the valve so it stays closed when it’s letting blood out of that section of the heart.”

Joe’s symptoms at the time of the surgery suggested he might have Marfan syndrome and a genetic test

GOSH Charity. One is ‘user acceptance in the age of technologically augmented healthcare’. This is looking at how best to evaluate these technologies with clinical teams in their work environment. It also includes studying the role of human values and trust in these developing technologies, which will eventually boost healthcare interactions and provide safer care for future technologies.

Another area of support includes data science projects, where a PhD student is currently working jointly with the University of Toronto on a patient-centred tool to characterise disease severity in cystic fibrosis. “The study will be looking at large amounts of data on children with the condition to see whether we can use machine learning to develop a ‘health score’ that will give a better overall measure of a child’s health,” Professor Sebire says. “Another study is about to start on causal inference, which is taking a large amount of *This took place before the COVID-19 pandemic

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To plan for the operation, surgeons created a 3D model of Joe’s heart and used VR technology to examine the site of the procedure.

Melanie remembers the impact it had on the whole family. “The VR software enabled us to put goggles on, use two hand controllers and feel as if we were moving through Joe’s heart, which was absolutely amazing,” she says. “We all had a go. You could travel through Joe’s heart and the aorta. It was mind blowing. His surgeon used that VR footage as well to minimise any surprises and look at the heart from every possible angle.”

Joe is currently doing well, has just moved into Year 13 at school and is aiming to go on to university.

“His transition to adult care at St Barts Hospital has been smooth, with a joint appointment a year ago with his GOSH and St Barts consultants. He’s also had his first visit to St Barts, which showed his heart and aorta were all normal,” Melanie says. “Our whole experience of GOSH was extremely positive with plenty of support and incredible expertise.”

data in a population, knowing different patients were treated in different ways but outside a clinical trial.

Then asking, can you use machine learning to start creating knowledge that humans wouldn’t have, about how a particular treatment affects disease outcome?”

Partnerships and knowledge collaboration are clearly an essential factor for DRIVE. The unit already supports joint-funded PhD students with the national health data science institute Health Data Research UK, the Turing Institute, the UCL Centre for Doctoral Training in Interactive AI at Bristol University, Cambridge University and Manchester University. It also works with undergraduate computer science students at University College London through its Industry Exchange Network and has partnered with Microsoft, IBM, ARM and NTT Data.

for all their future visits,” he adds. “There’s still a lot of work to be done on how you manage the workflow of all these digital tools, but this could be a big change for how patients and staff interact with the hospital.

“What we want to do with the CIRP is to build clinically useful tools for GOSH. Even once you’ve built a tool, you can’t suddenly use it on patients, it has to go through an evaluation process. We’ve appointed an academic clinical lecturer, whose role will be to do that evaluation piece, taking it to clinicians and patients and asking them how they would use these technologies.

“Ultimately, we want everything we do to be judged on whether there’s patient benefit.”

TEAMING UP WITH YOUNG PEOPLE Yet DRIVE’s partnerships extend beyond academic and corporate partners to one very important group; the patients themselves. By engaging with GOSH’s Young Person’s Advisory Group (YPAG) directly, specifically around AI, it is discovering first-hand how technology can improve patient experience.

“We’re asking questions such as would children and young people use AI differently to adults?” Professor Sebire points out. “This has been a real eye opener as to what they’d accept. For example, the idea of having a robot nurse didn’t go down well but a device that would alert them to their medication dose being low was a good thing. We need to work with children and young people to discover what’s acceptable to them and keep that at the centre of technology development.”

Professor Sebire acknowledges there’s still a lot more to explore in AI and VR technology in the healthcare arena. “Working with YPAG has shown us that this current generation of young people have grown up with photo-realistic games and TV, so they have high expectations around graphics,” he says. “We realised early on that VR content needs to be much better quality than perhaps an adult would expect. There’s certainly potential with AI, VR and gamification; they will be significant areas to explore in the future. As an organisation we’re never going to be making that content but someone could and that’s where we need partners.”

CLINICAL INFORMATICS RESEARCH PROGRAMME - THE NEXT STEPS As Professor Sebire explained, CIRP’s focus will be on machine learning and how data can be used most effectively; for example, work is about to start on evaluating digital stethoscopes, while another area of development will be around remote monitoring. “We’ll be looking at whether we need to see patients on site

RECENT DIGITAL INNOVATIONS ENHANCING THE PATIENT EXPERIENCE Heads Up – patients and families can log on the MyGOSH app and submit questions they’d like to ask before appointments, which also gives doctors an idea of what they’re going to be asked.

Fingerprint – within Epic, captures the likes and dislikes of a patient so doctors and nurses can engage with them on a personal level.

Essence – similar to a private messaging board, but for clinicians. Clinicians write many notes on a patient, this provides a short narrative for quick updates, with links to the more comprehensive notes.

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WHY I SUPPORT THE CHARITY

Ivy in her mountain gear, ready to climb her 'Everest'

In the run up to her 100th birthday last month, keen walker Ivy Richmond took on her very own Everest Challenge to raise money for GOSH Charity. Ivy shares her special story with Pioneer.

A love of walking begins From an early age, walking everywhere was normal. It was the only way for my two older brothers, George and Frank, and I to get to our school in north London, and back again, twice each day. But we loved being outside walking – playing marbles in the street with friends was another of our favourite activities.

In 1932 I transferred to secondary school but then a move of home meant a move in school, where I wasn’t very happy. Even though money was tight, my mother saved to send me to Pitman’s College to learn shorthand and typing skills (I still use shorthand when needing to write in a hurry). After the year-long course, I was employed as an office junior at the Commercial Union in London’s Lower Regent Street, earning 30 shillings a week. That was just enough for any travel I needed and be able to give my mother some money too. But all this time I still loved walking around whenever I could.

A connection with GOSH My brother Frank’s wife Joan gave birth to their first daughter on 17th February 1944. Margaret (Miggie) was born with a deficiency in her white blood corpuscles, making it difficult for her to fight disease. As luck would have it, Miggie stayed one step ahead of antibiotics development and was well looked after by Great Ormond Street Hospital (GOSH), where she spent a great deal of her childhood.

By this time, I was working at a mineral water company called Idris, based in Camden Town, so I was able to visit Miggie at GOSH twice a week after work – it was around a 40-minute walk. Back then there were times set for visiting; once I was told off by a nurse because I had arrived too early, something that the less strict nurses had always allowed! I got to know GOSH well between the years of 1944 and 1960, before Miggie was transferred to University College Hospital.

Miggie was such a kind-hearted, sweet child and I loved her very much. Her determination and wonderful care at GOSH and other NHS providers gave her the best possible quality of life for 31 years. That’s why our family have continued to support GOSH and raising money for Great Ormond Street Hospital Children’s Charity (GOSH Charity) became the obvious choice when I set myself my ‘100th-Year Challenge’. I’d also been inspired by what Captain Sir Tom Moore had achieved; if only I could raise as much money as he did!

Ivy’s niece Miggie (right) at GOSH

The 100th-year challenge My youngest niece and her partner climbed to the summit of Mount Everest in 2009 and they suggested I could do the same with my own ‘Everest’ in my 100th year. I was set up with a chart to record the flights of stairs I would climb; nine sets of 18 stairs per day for 364 days, plus a diagram to show the landmarks along the way.

I have always enjoyed walking in the hills. I trekked to a high hut on the Marmolada in Italy when I was in my fifties and I also climbed Snowdon in Wales, which must have been really good practice for what I’ve recently been doing.

My first feat of the challenge was Box Hill (224 metres = 78 flights of stairs), which was the local hill to where I had lived for many years in Epsom, Surrey. I then passed over the National Three Peaks (the heights of Scafell Pike in the Lake District, Ben Nevis in Scotland and Snowdon in Wales) and Mont Blanc in France, on my way to the Seven Summits, which are the highest points in each continent. As I talk to Pioneer, I am above Camp 4 on Everest. By the day before my 100th birthday on 23rd October, I was on top of the world (8848m = 3,073 flights of stairs). I felt elated to be at the summit of Everest…also because I won’t have to climb nine flights of stairs in a row every day!

Walking has always been my passion as keeping fit is important to me – sometimes I still feel as if I’m 21 – and I’m convinced it’s vital to just keep going. When I lived in Epsom I belonged to a local walking group until the age of 96, before I moved to Ipswich, and I loved our walks on the South Downs. I also love trips to the Suffolk and Norfolk coasts and am looking forward to my trip to Cornwall in November.

Most of all, I’m thrilled that my stair climbing has raised money for such a good cause and thank everyone for their support. What I would really like now is an exercise bike so I can start my next challenge cycling the distance between Land’s End and John O’Groats!

Cycling could be my 101st year challenge to raise money...watch this space.

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GOSH JOINS GLOBAL COLLABORATION ON GENOMICS Sharing knowledge, expertise and data with international colleagues will pave the way to better treatments for children.

Pioneer finds out more.

Of the more than 7,000 rare diseases that affect millions of individuals globally, only a few hundred have approved treatments. Many of these diseases either affect children their whole lives, or may lead to early death from complications, sometimes just a day after birth.

More than 28,000 children with rare diseases are treated at Great Ormond Street Hospital (GOSH) – but it’s international collaborations that can really boost the search for treatments .

To help achieve this, GOSH joined forces with three other leading children’s research institutions earlier this year to decipher paediatric illnesses, including rare diseases, and find better treatments.

GOSH, alongside UCL Great Ormond Street Institute for Child Health (ICH), is now working with Boston Children’s Hospital, the Murdoch Children’s Research Institute with The Royal Children’s Hospital in Melbourne, and The Hospital for Sick Children (SickKids) in Toronto to evaluate genomic data, clinical data from patients, and scientific and medical expertise to accelerate the discovery and therapeutic development.

The partnership, known as the International Precision Child Health Partnership (IPCHiP), is the first major global collaboration around genomics and child health and it’s hoped that additional institutions will join the collaboration in the future.

THE GOAL IPCHiP aims to enable the world’s top experts in paediatrics and genomics to work together to improve diagnosis, implement personalised treatment decisions and develop new therapeutic targets and treatments that will benefit children around the world.

“Our partnership will enable us to combine the collective power of our research effort to answer questions about rare diseases in children, which we’re not able to answer by working only within our own centres,” ICH Director Professor Rosalind Smyth 32 PIONEER

explains. “This will mean that we can move much more swiftly to effective treatments where none currently exist.”

GLOBAL IMPACT IPCHiP’s first project involves epilepsy in infants, bringing together efforts already underway at the four hospitals.

For the project – entitled GeneSteps – investigators at each site will enrol babies under age one with epilepsy, sequence their genomes, change treatment based on the findings when appropriate and follow the children’s development long term. No patient will be identifiable from the data used and no patient data will be shared across international borders.

The study will compare those who receive a genetic diagnosis with those who don’t. Through this project, IPCHiP will establish systems to evaluate data responsibly across the different institutions.

“We know that for at least 50% of babies with epilepsy, there is a genetic cause,” ICH Principal Research Fellow Dr Amy McTague says, who is leading GeneSteps in the UK.“ For some, having a specific genetic diagnosis can change treatment and we want to know if finding the genetic problem earlier improves epilepsy and development in the long term.”

The study will pioneer the use of rapid genome testing in epilepsy and will recruit 100 babies initially, with a larger study planned.

“This world-first collaboration, supported by the GOSH National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) and charity Young Epilepsy, is a unique opportunity for us to work together for patients with rare diseases such as genetic epilepsy,” GOSH Honorary Consultant in Paediatric Neurology, President-elect of the International League Against Epilepsy and an investigator on the project Professor Helen Cross adds. “This exemplifies GOSH’s ambition to be a research hospital, where research is

Our partnership will enable us to combine the collective power of our research effort to answer questions about rare diseases in children, which we’re not able to answer by working only within our own centres. embedded across our care of children with rare and complex diseases. GOSH’s Zayed Centre for Research into Rare Disease in Children, where Dr McTague is based, also allows our work to draw from expertise at ICH and GOSH, while the hospital’s global reputation means we will be able to work with a large number of children and their families.”

A later project will involve complex genetic disorders in the neonatal intensive care unit and paediatric ICU, and other projects will follow in the future too.

“We’re bringing together the world’s top experts in genomics, rare disease, paediatric medicine, and computational science to develop precision approaches to benefit children everywhere,” Professor Smyth adds. “In addition, we think our large patient cohorts will enable partnership with industry when a discovery advances to clinical trials.”

After initial seed funding by each institution, the partnership anticipates additional funding through national health and medical research grants within each country, industry contracts, and philanthropic efforts. The collaborative has also received support from the International Venture Philanthropy Network.

Turn to page 22 for more on the Zayed Centre for Research.

LUCIA’S STORY Lucia, 14, from London, was diagnosed with SCN8A-related epilepsy at GOSH after taking part in genetic testing.

“Lucia’s early life was consumed by lengthy periods of near-constant seizures,” mum Katherine says.

“The years were spent living on hospital wards and on intensive care units, consumed by searching for answers to a condition that was unresponsive to an endless stream of medicines and treatments.

“Finally, when Lucia was nine years old her condition was identified through a genetic test that had only recently become available. With this diagnosis the right medicine could be prescribed – a sodium channel blocker – and almost immediately Lucia’s seizures stopped. For the first time in her life, Lucia began to feel peace. And finally, we felt a different peace that comes from the end of a long and painful struggle for answers.

“Now 14 years old, Lucia provides all who know her with happiness and love. And while we navigate the many challenges that her disabilities naturally present, we understand the value of having a diagnosis, not only on Lucia’s quality of life, but the wellbeing of her family responsible for her ongoing care.

“We stand in solidarity with all those who have endured similar, or greater, periods of ‘not knowing’ and advocate for the funding and support toward dedicated genetic testing at the moment of a young patient’s presentation; a focus group tenaciously committed to diagnostics and ongoing testing.

Because the nine years that Lucia waited for her diagnosis cost her, and her family, infinitely more than pain and heartache.”

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PARENT’S PERSPECTIVE Max first came to GOSH when he was just a few months old, after doctors discovered he was profoundly deaf. Mum Giulia tells Pioneer his story.

Finding out Max was deaf when he was tiny was a real shock. He must’ve only been about a month old.

We also learnt that Max’s condition had a genetic cause and, through testing, realised that myself and my husband had a faulty gene, giving us a onein-four chance of having deaf children. When our younger daughter Olivia was also born deaf, we were devastated.

At the time, Max was fitted with hearing aids at his local hospital, but he still couldn’t hear much with them.

Due to his level of deafness, he was referred to Great Ormond Street Hospital (GOSH). As Olivia was found to be moderately deaf, she didn’t need to come to GOSH. I was quite naïve when we were first transferred to GOSH. I was happy we were there, but it was a reality I wasn’t used to. Everything was so new; there were a lot of emotions.

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It was also scary knowing Max would need to go through such a big operation so young but understanding what benefits the implants bring gave us hope for his future.

A LIFE-CHANGING OPERATION A month after his first birthday Max finally came to GOSH to have his cochlear implants fitted. It was a big operation, lasting six hours, but a successful one.

After the operation, I stayed overnight with Max on Peter Pan Ward. We had our own room and there were lots of other parents staying over too, so it was nice to not be completely alone. The Play team would also bring Max toys; I remember his cot was full of them. He was only small but I’m sure he enjoyed it very much at the time.

“For families coming to GOSH for the first time, I would say you’re in absolutely the right place and your children will be taken great care of. I think it’s one of the best hospitals in the country.”

Then, two weeks later, Max’s implants were switched on and from then our journey really began. GOSH explained it was like trying to fine-tune a radio, where you hear a lot of sounds, but the frequency isn’t quite right. The implants don’t restore normal hearing; instead, they give a deaf person a useful representation of sounds in the environment.

It’s through speech and language therapy that you help a child with implants to listen correctly and understand the new sounds they hear. We did the speech and language therapy with Auditory Verbal UK. It was hard work but also a lot of fun because it was all play based.

MAX TODAY Now seven years old, Max is doing really well. He’s incredibly active and energetic – just like Tigger from Winnie the Pooh, always bouncing around!

I don’t think Max even notices the difference the implants have made because he only really lost a year of hearing. The first thing he does when he wakes up is chat to you, so it’s easy to forget he’s wearing implants.

Having said that, he is deaf, so there are things we need to be mindful of.

When you first find out your child has a disability it’s difficult, so being able to meet other parents and see other children going through similar experiences is always helpful. I almost cried the first time I saw a child with cochlear implants talking because I didn’t really know what implants were. Having the new Sight and Sound Centre will help with that.

A MESSAGE FOR GOSH FAMILIES For families coming to GOSH for the first time, I would say you’re in absolutely the right place and your children will be taken great care of. I think it’s one of the best hospitals in the country.

One of the things I love most about GOSH is that Max’s team haven’t really changed since he was 10 months old and they’ll continue to follow his progress until he’s an adult. The Play team is great too and crucial in any children’s hospital for lifting the children’s spirits and supporting the parents.

I’ll be forever grateful to GOSH because it gave Max his hearing; now he can communicate with everyone. *The Sight and Sound Centre is the UK’s first dedicated medical facility for children and young people with sight and hearing loss. Housed in the building formerly known as the Italian Hospital, Great Ormond Street Hospital Children’s Charity pledged £25 million towards the completion of the centre, with support from a range of generous donors including Premier Inn. Sight and hearing specialties are co-located, meaning better multi-disciplinary working, in a building designed to meet the specific needs of children with sensory loss.

He gets more tired than other children because he has to focus in a different way, but he goes to a mainstream primary school with a deaf unit, so I imagine seeing other children who are deaf helps because it’s kind of their normal.

Max also got his new Marvels – a type of speech processor for his implants – from advanced bionics this year. They give him a better quality of hearing and connect to Bluetooth, meaning he can stream phone calls, TV programmes and music all through his ears!

COMING TO THE NEW SIGHT AND SOUND CENTRE*, SUPPORTED BY PREMIER INN Max only goes to GOSH around once a year for a check-up now. We were very lucky to have our last appointment at its new Sight and Sound Centre too, which is amazing. The building is spectacular, and a real testament to how much care goes into treating children with sensory conditions. I imagine for a parent going there for the first time, it also feels very reassuring.

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Great Ormond Street Hospital Children’s Charity 40 Bernard Street London WC1N 1LE 020 3841 3131 gosh.org Great Ormond Street Hospital Children’s Charity. Registered charity no. 1160024.

Thank you to all the patients, families and staff who took part in creating this edition of Pioneer.

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