Podcasts about clinical lead

In this week's episode of the Full of Beans Podcast, I'm joined by the incredible Dr. Amy Harrison, Clinical Psychologist, Associate Professor at UCL, and Clinical Lead at Altum Health. With over 13 years of experience across inpatient, day, and outpatient settings, Amy brings a wealth of expertise and warmth to her work supporting young people with eating disorders.Together, we take a deep dive into Family-Based Treatment (FBT), a powerful, evidence-based approach designed to help children and adolescents recover in the community with the support of their families.Key TakeawaysWhat Family-Based Treatment (FBT) is and how it worksWho FBT is designed for and how it supports younger individualsThe structure and goals of FBT across different stages of treatmentWhy involving someone's family as support is central to recoveryDebunking myths: FBT does not blame parentsChallenges of FBT and how to navigate resistance and emotional distressHow clinicians can get trained in FBT (including Amy's upcoming training with Altum Health)Timestamps:06:30 – What is Family-Based Treatment (FBT)?10:15 – Who FBT is suitable for (and who it may not fit)13:50 – Reintegrating autonomy after initial food support17:30 – Looking beyond food: feelings, systems & communication22:40 – Common challenges families and clinicians face27:20 – Advice for clinicians seeking FBT training30:00 – The power of collaboration in recoveryTrigger warning: This episode discusses eating disorders, suicidal ideation and assisted dying.Connect with Us:Subscribe to the Full of Beans Podcast hereFollow Full of Beans on Instagram hereConnect with Amy and Altum Health:Amy's LinkedInAltum Health on LinkedInAltum Health on InstagramRead our latest blog hereFurther Resources: First Steps EDThank you for listening and being part of this important conversation!If you loved this episode, don't forget to subscribe, leave a review, and share it with someone who might benefit!Sending positive beans your way, Han

In this episode of The Patient From Hell, host Samira Daswani speaks with oncology pharmacist Megan Hartranft about the critical role of oncology pharmacists in cancer care. They discuss the unique responsibilities of oncology pharmacists, the importance of patient education, and the growing field of oral chemotherapy. Megan shares insights on medication adherence, the use of mobile health technologies, and the significance of symptom management in improving patient outcomes. The conversation highlights the need for better integration within healthcare systems and offers practical tips for patients navigating their treatment journey.About Our Guest:Dr. Megan Hartranft is a Clinical Lead with the Clinical and Digital Solutions team, advising on precision oncology products.Prior to joining Labcorp, Dr. Hartranft was a Field Medical Scientific Associate Director at Sanofi, in charge of training for the hematology-oncology medical science liaison team. Earlier as a practicing clinician, she established an oral chemotherapy education program and participated in interprofessional clinics at Rush University Cancer Center. She has also spent time in academia as the oncology faculty member at Rosalind Franklin University of Medicine and Health Sciences, where she maintains an adjunct appointment. Dr. Hartranft is active in several professional organizations, including her roles on the Hematology Oncology Pharmacy Association's Public Policy & Advocacy Committee as well as the American Society of Health System Pharmacy Section of Pharmacy Informatics and Technology Clinical Decision Support and Analytics Advisory Group.BS in Biochemistry/Molecular Biology and BA in Classical Studies - Michigan State University Doctor of Pharmacy - University of North Carolina at Chapel Hill PGY1 Pharmacy Residency - University of Michigan PGY2 Oncology Specialty Residency - University of Georgia/Augusta University Health SystemResources & Links:This episode was supported by the Patient Centered Outcomes Research Institute (PCORI) and features the PCORI research study here: https://pubmed.ncbi.nlm.nih.gov/30964... ‘Integrating Advance Care Planning Videos into Surgical Oncologic Care: A Randomized Clinical Trial'00:00 Introduction to Oncology Pharmacy02:49 The Role of Oncology Pharmacists in Patient Care06:03 Patient Interaction and Education09:09 Exploring Oral Chemotherapy11:45 Adherence to Oral Anti-Cancer Medications15:01 Mobile Health Technologies in Oncology17:58 Symptom Management and Patient Support21:11 The Future of Oncology Pharmacy24:09 Final Thoughts and Tips for PatientsConnect with Us:Enjoyed this episode? Make sure to subscribe, rate, and review! Follow us on Instagram, Facebook, or Linkedin @mantacares and visit our website at mantacares.com for more episodes and updates.Listen Elsewhere: Website: https://mantacares.com/pages/podcast?... YouTube: https://www.youtube.com/@mantacares Spotify: https://open.spotify.com/episode/3TR1... Apple: https://podcasts.apple.com/us/podcast... Disclaimer:All content and information provided in connection with Manta Cares is solely intended for informational and educational purposes only. This content and information is not intended to be a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.This episode was supported by an award from the Patient-Centered Outcomes Research Institute.

Today we're diving into the latest findings from the AXA Mind Health Report, with a special focus on what they mean for Irish workplaces. The report, drawing on the experiences of 17,000 participants across 16 countries, reveals that Ireland now ranks at the bottom of the EU for overall mental health-an alarming statistic, with nearly half of Irish adults reporting they are struggling or languishing. For HR managers and organisational leaders, the findings are particularly relevant too – so let's explore them! To take us through the findings and what this all means for you and your organisation, we're delighted to be joined by Nicole Paulie, Chartered Psychologist and Clinical Lead at laya healthcare's 24/7 Wellbeing Support Programme.    In this episode we cover... 00:00 Understanding the AXA Mind Health Report 03:46 The Gap Between Employer Perception and Employee Reality 07:50 Impact of Mental Health on Workplace Performance 15:10 Trends in Mental Health and Future Outlook 19:54 Practical Steps for Organisations to Support Mental Health   Explore the findings and the full report at www.layahealthcare.ie/mind-health/   About The HR Room Podcast The HR Room Podcast is a series from Insight HR where we talk to business leaders from around Ireland and share advice what's important to you as a HR professional, an employer or people leader.  If you are enjoying these episodes, do please feel free to share them with colleagues, friends and family. And even better, if you can leave us a review, we'd really appreciate it! We love your feedback, we take requests, and we're also here to help with any HR challenges you may have! Requests, feedback and guest suggestions

Weight loss drugs can delay diseases associated with ageing and halve deaths caused by heart attacks, according to researchers at the European Congress of Obesity. We discuss this further with Donal O'Shea, Clinical Lead for Obesity at the HSE.

Weight loss drugs can delay diseases associated with ageing and halve deaths caused by heart attacks, according to researchers at the European Congress of Obesity. We discuss this further with Donal O'Shea, Clinical Lead for Obesity at the HSE.

In this episode, I speak with Professor Guy Leschziner, a consultant neurologist and author of three bestselling books, including: “The Man Who Tasted Words”, “The Secret World of Sleep”, and “The Seven Deadly Sins”, which this interview focuses on. Drawing on insights from evolutionary biology, genetics, and clinical neurology, Guy makes a compelling case that what we label as “sin” may often have a biological cause, and isn't necessarily a moral failing. Expect to learn: — Why our so-called “sins” evolved as adaptive traits—and why they still serve a purpose — How free will may be more of a spectrum than a binary — Why understanding the biology of behaviour could radically change the criminal justice system — The disturbing story of Robert Alton Harris—and what it reveals about judgment, compassion, and accountability And more. You can learn more about Guy's work at https://www.guyleschziner.com. --- Dr Guy Leschziner is a neurologist with special expertise in sleep disorders and epilepsy. Dr Leschziner is Consultant Neurologist at London Bridge Hospital and Clinical Lead for the Sleep Disorders Centre at Guy's and St Thomas' Hospital, London, one of the largest sleep units in Europe. He also practices at London Bridge Hospital and the Cromwell Hospital. He is also Reader in Neurology at the Department of Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London. Under the broad umbrella of sleep disorders, Dr Leschziner is a particular authority on narcolepsy, sleepwalking, Kleine-Levin syndrome and restless legs syndrome. Dr Leschziner is also enthusiastically engaged with public education through a wide range of media work. He presented a popular radio series for the BBC, Mysteries of Sleep, as well as The Secrets of Sleep for Channel 4 television in the UK. He has also been an expert commentator for BBC News and The Guardian. Dr Leschziner is also the author of several books: The Nocturnal Brain: Nightmares, Neuroscience and the Secret World of Sleep, The Man Who Tasted Words, and The Seven Deadly Sins. --- Interview Links: — Dr. Leschziner's website - https://www.guyleschziner.com — Dr. Leschziner's books: https://amzn.to/4dbnFru

In this piece we discuss blood management in emergency and elective surgery with Matthew Wiles, an anaesthetist from Sheffield, UK, and editor of the journal Anaesthesia, and Catherine Downs, an anaesthetist from Sydney, Australia. The episode delves into haemorrhage associated with trauma and major surgery, and the benefits of point of care testing. We also took the opportunity to discuss authorship of scholarly work and the need to support emerging researchers and site collaborators. Presented by Andy Cumpstey and Kate Leslie on location at the Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine in Cairns, Australia, with their guests, Dr Matthew Wiles, Consultant Anaesthetist and Clinical Lead for Major Trauma, Sheffield Hospitals NHS Foundation Trust, and Honorary Senior Clinical Lecturer, Sheffield University, Sheffield, UK, and Dr Catherine Downs, Consultant Anaesthetist, Prince of Wales Hospital, and Senior Lecturer, Randwick Clinical Campus, University of New South Wales, Sydney, Australia

How are we generating possibilities in every moment?...Rana Kökçinar is a Systemic Psychotherapist and Family Therapist working on unceded Kaurna Land, South Australia.Anokh Goodman is a Systemic Psychotherapist, Clinical Lead and Training Consultant with Sikh heritage and a working-class background, living in Leeds, North England. Passionate about relationships, narratives, social justice, poetry, and spoken word, he brings an intersectional lens to his work, exploring ideas of radical love to foster inclusive, culturally responsive change. Through deep listening and dialogue, he believes untold stories can transform how we heal, connect, and reimagine our world.Today, Abbie, Rana, and Anokh explore the ideas of super-coherence and incoherence; the beautiful emergence of transient interactions; changes in moving from a loop of 'doing' and ‘having' to a state of ‘being;' and ongoing de/re-construction of the scenery  of our social worlds....Stories Lived. Stories Told. is created, produced & hosted by Abbie VanMeter.Stories Lived. Stories Told. is an initiative of the CMM Institute for Personal and Social Evolution....Music for Stories Lived. Stories Told. is created by Rik Spann....⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Explore all things Stories Lived. Stories Told. here⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠.Explore all things CMM Institute here.

Send us a textWelcome to the fifth episode of season five, in conversation with Professor Pranav Pandya. Professor Pandya's Bio:Professor Pranav P PandyaBSc MBBS MD FRCOGConsultant in Fetal MedicinePranav Pandya is a Professor in Fetal Medicine at University College London. He is currently the Director and Clinical Lead of Fetal Medicine services at University College London Hospitals.Pranav is dedicated to caring for pregnant women and in particular the well-being of their baby. His expertise is in the ultrasound examination of the mother and unborn baby(s) with particular interest in first trimester anomalies, fetal cardiology, surgical anomalies and fetal therapy.Pranav is also the Chair of the Fetal Anomaly Screening Programme Advisory Group at the UK National Screening Committee, where he is involved in developing and implementing national policy on fetal anomaly scanning and screening for fetal aneuploidy and implementation of cell free fetal DNA within the NHS.He has published extensively in the field of fetal medicine and is Editor in Chief of a major textbook - Fetal Medicine Basic Science and Clinical Practice.Podcast information:We have not included any patient identifiable information, and this podcast is intended for professional education rather than patient information (although welcome anyone interested in the field to listen). Please get in touch with feedback or suggestions for future guests or topics: conversationsinfetalmed@gmail.com, or via Twitter (X), Bluesky or Instagram via @fetalmedcast.Music by Crowander ('Acoustic romance') used under creative commons licence. Podcast created, hosted and edited by Dr Jane Currie.

James' Place provides free, life-saving therapy for men in suicidal crisis. We were invited to their London centre to speak with Dan Bracken, Clinical Lead and Psychotherapist, about the urgent issue of male suicide. In this episode, we explore how James' Place supports men in crisis and the impact of their work.

Adam Cox is joined by Kevin Joshua – the Clinical Lead and Superintendent Pharmacist at My Juniper, a weight loss medication service. They talk about the UK's ongoing obesity crisis, how much of obesisty is down to genes and how much is down to life choices. They also talk about this new rise in weight loss medications and how they, alongside traditional weight loss techniques, are looking like promising solutions to the problem. 

This month we focus on bone health with the help of our guest Dr Alistair Mackett, a Consultant Geriatrician specialising in Parkinson's at Addenbrookes Hospital in Cambridge and Regional Clinical Lead for the East of England Parkinson's Excellence Network.  People with Parkinson's are far more likely to to have poor bone health and a far higher risk of fracture than the rest of the population. We find out why, how this can be prevented and what treatments are available.   Parkinson's Excellence Network https://www.parkinsons.org.uk/professionals/parkinsons-uk-excellence-network , Parkinson's UK Bone Health https://www.parkinsons.org.uk/information-and-support/your-magazine/experts/bone-health-and-parkinsons        

Jennifer Landingin tells Charlie McGinley about how she suffered a stroke at the age of 46 while working as a nurse and Professor Joe Harbison, Clinical Lead for the Irish National Audit of Stroke discusses the findings of the INAS National Report 2023.

In this episode, Dr Mike O'Callaghan takes us into the fascinating world of GP data, an area that enables us to learn more about the impact of general practice on Irish healthcare. Formerly with Intel, Mike changed career to general practice and works in a busy practice in Bruff, Co. Limerick, juggling this with his role as the Clinical Lead in the Research, Policy and Information Department of the College. To contact the podcast, email us at media@icgp.ie Find out more about the Irish College of GPs at www.irishcollegeofgps.ie

Rare condition research is evolving, and patient communities are driving the breakthrough. In this special Rare Disease Day episode, we explore the challenges and opportunities shaping the future of rare condition therapies. From groundbreaking gene therapy trials to the power of patient-driven research, our guests discuss how collaboration between families, clinicians, researchers, and regulators is paving the way for faster diagnoses, equitable access to treatments, and innovative approaches like nucleic acid therapies and CRISPR gene editing. With insights from Myotubular Trust, we follow the journey of family-led patient communities and their impact on advancing gene therapy for myotubular myopathy - showcasing how lived experience is shaping the future of medicine. However, while patient-driven initiatives have led to incredible progress, not every family has the time, resources, or networks to lead these research efforts. Our guests discuss initiatives like the UK Platform for Nucleic Acid Therapies (UPNAT), which aims to streamline the development of innovative treatments and ensure equitable access for everyone impacted by rare conditions. Our host Dr Ana Lisa Tavares, Clinical lead for rare disease at Genomics England, is joined by Meriel McEntagart, Clinical lead for rare disease technologies at Genomics England, Anne Lennox, Founder and CEO of Myotubular Trust and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at University of Oxford. "My dream is in 5 to 10 years time, an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested. And at that exact time, the day of the diagnosis becomes also a day of hope, in a way, where immediately the researcher that sent the genetics lab flags that specific variant or specific mutations. We know exactly which is the best genetic therapy to go after." You can download the transcript, or read it below. Ana Lisa: Welcome to Behind the Genes.    [Music plays]  Anne: What we've understood is that the knowledge and experience of families and patients is even more vital than we've all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family, they would tell you, “Yes, my son has had the odd liver result.”  There were some very serious liver complications but everybody thought that was a minor issue, but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing.  [Music plays]  Ana Lisa: My name is Ana Lisa Tavares, I'm Clinical Lead for Rare Disease research at Genomics England and your host for this episode of Behind the Genes. Today I'm joined by Anne Lennox, Founder and CEO of the Myotubular Trust, Dr Meriel McEntagart, an NHS consultant and Clinical Lead for Rare Disease Technologies at Genomics England, and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at the University of Oxford.    Today we'll be hearing about the importance of involving the patient community, particularly as new rare therapies are developed, and discussing the forward-facing work that's happening that could have potential to unlock novel treatments for many rare conditions.  If you enjoy today's episode we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. Thank you so much for joining me today.  Please could you introduce yourselves.   Anne: I'm Anne Lennox, I'm one of the founders of the Myotubular Trust, a charity that raises research funds for and supports families affected by the rare genetic neuromuscular disorder myotubular myopathy.  Meriel: I'm Meriel McEntagart, I'm a consultant in clinical genetics in the NHS and I have a special interest in neurogenic and neuromuscular conditions.  Carlo: Hi, I'm Carlo Rinaldi, I'm Professor of Molecular and Translational Neuroscience at the University of Oxford. I'm a clinician scientist juggling my time between the clinic and the lab where we try to understand mechanisms of diseases to develop treatments for these conditions.  And I'm also here as a representative of the UK Platform for Nucleic Acid Therapies, UPNAT. Thanks for your invitation, I'm very pleased to be here.  Ana Lisa: Thank you. Meriel, I'd love you to tell us a bit about your work and how you met Anne, how did this story start?  Meriel: Thank you. Well prior to being a consultant in clinical genetics, I spent 2 years as a clinical research fellow in neuromuscular conditions, and as part of that training I worked on a project where the gene for myotubular myopathy had just been identified, and so there was a big international effort to try and come up with sort of a registry of all the genetic variants that had been found as well as all the clinical symptoms that the affected patients had, and then do kind of a correlation of the particular variant mutation with symptoms.   I worked when I was training to be a clinical geneticist because of my interest in neuromuscular conditions so when I eventually became a consultant at St George's Hospital I was actually interviewed by the Professor of Paediatrics and he knew Anne and her son, when Anne was looking for more information about the condition he suggested that perhaps I might be a good person for Anne to talk to.  Ana Lisa: Thank you. Interesting connections. Anne, can you tell us your story and how this led you to found the Myotubular Trust?  Anne: Yes, thanks Ana-Lisa.  Well, as many families will tell you when they're newly diagnosed with a rare disease, you go from knowing nothing about a condition to being one of the few deep experts in that condition because there are so few deep experts. So this happened to us in 2003 when our son, Tom, was born, and when he was born he was floppy and his Apgar scores, the scores they do on new-born babies, were pretty poor, and before long we knew that it was more than just momentary issues at birth.  And, cutting a very long story short, 5 weeks later he was diagnosed with this very rare neuromuscular genetic disorder that we didn't know we had in the family.  We were told that this was a very serious diagnosis.    At that time – more than 20 years ago – over 80% of those boys didn't make it to their first birthday and the stark statistic we had in our head a lot was that only 1% made it past the age of 10. And that has changed due to better ventilator and breathing equipment, etc, but at the time we expected that he might not make it to his first birthday.    We were very lucky, we had Tom longer than one year, we had him for nearly 4 years, 4 very lovely years where it was tough, but he was a really lovely member of our family.  Despite being really weak he managed to be incredibly cheeky and bossy, and he was a great little brother for his big sister. We were also very lucky that he was being looked after by Professor Francesco Muntoni, who is Head of the Paediatric Neuromuscular Service at Great Ormond Street. And, like Carlo, he is a clinical researcher and actually that I found to be amazing as a family member because you knew what was happening out there and Professor Muntoni, other than living with the reality day to day you want to know where things are going.    We began to realise that back then 20 years ago the more common rare neuromuscular diseases were finally beginning to get some fundamental research funds, like Duchenne, spinal muscular atrophy, and Professor Muntoni was very good at explaining to lay non-scientific parents like us that one day the technologies that would lead to a cure, that would re-engage proteins for other conditions and would translate down eventually into the possibility of replacing myotubularin, which is the protein not being produced or not being produced enough in myotubular myopathy. And then we began to understand actually what the barriers to that would be, that translating developments in more common, or let's say more prevalent conditions, would be hard to do without some translation research being done; you could not just not lag years behind, you could lag decades behind if you haven't done some other work.    So, I met Wendy Hughes, another mother, of a boy called Zak who was a few years older than Tom, and these were the days before social media, and it was amazing to be in contact with another family going through something similar and we had great conversations. But then they were also looked after by Professor Muntoni and we particularly began to develop the idea as 2 families that we might be able to raise some research funds towards this concept of keeping pace with the scientific developments.  And then we discovered there was no charity we could channel those funds through. Even the umbrella body for neuromuscular diseases who were covering 30 to 40 conditions, frankly, they just couldn't trickle their funding down into investing in every neuromuscular disease, and slowly but surely it dawned on us that if we did want to make that difference we were going to have to set up our own charity.   So that's what we eventually did and back in 2006, we founded what was actually the first charity in Europe dedicated to myotubular myopathy – luckily, more have come along since – and we were dedicated to raising research funding. In fact, it wasn't our goal to set up another charity but around that time, about a year in, we happened to go to a meeting where the Head of the MRC, the Medical Research Council, was giving a talk and he said that in the last few years the MRC had begun to really realise that they couldn't cure everything, that they couldn't cure the diseases that would be cured in the next millennium from a top down perspective. There had to be a trick, there had to be a bottom up as well, because that was the only way this was going to happen. And I have to say that that was a really reassuring moment in time for us to realise that we weren't just chasing pipe dreams and trying to do something impossible, that there was a role for us.    Ana Lisa: I think it would be really interesting for people to hear your story and the amazing set-up and fundraising that you've done, and at the same time it would be really good for us to reflect on how this isn't feasible for every patient and every family and how we're going to need to work cooperatively to move forwards with rare therapies.  Anne: When we explored the idea with Professor Muntoni and Meriel and others about setting up a charity one of the really reassuring things that Professor Muntoni got across to us was that this wasn't about raising the millions and millions it would take to fund clinical trials but the issue in the rare disease space was funding the proof of principle work, the work where you take a scientist's hypothesis and take it over the line, and the rarer the disease, the less places there are for a scientist to take those ideas. And the example he gave us was a piece of research like that might cost a hundred to a couple of hundred thousand, if you fund a piece of work like that and if it is successful, if the scientist's principle gets proven, then behind you it's much easier for the bigger muscle disease charities to also invest in it. It's harder for them to spread their money across all the very rare diseases hypothesis out there, but if you've helped a scientist get over the line they'll come in behind you and then they won't be the ones who fund the tens of millions that it takes to run a clinical trial.    If it's got potential, then that's where the commercial world comes in, and that's where the biotechs come in. So he'd given the example of if you spent £ten0,000 on a piece of research and it actually is proven, in behind you will come the bigger charities that would put in the million that takes it to the next phase, and in behind them will come the bio-checks that'll provide biotechs that'll provide the tens of millions.    And then, you know, a lot of what happens relies on serendipity as well, we know that, and you could easily run away with the idea that you made everything happen but you don't, you stand on the shoulders of others. And our very first grant application in our first grant round, which received extraordinary peer review for how excellent the application was, was a £100,000 project for a 3-year project that had gene therapy at the core of it by a researcher called Dr Ana Buj Bello at Généthon in Paris. This piece of research was so promising that 18 months in she and another researcher were able to raise $780,000 and, as Professor Muntoni predicted, from the French muscle disease charity AFM and the American muscle diseases charity MDA.  And 18 months into that 3 years it was so promising that a biotech company was started up with $30 million funding, literally just on her work.    So that doesn't always happen but, as Professor Muntoni explained, our job was not that $30 million, our job was that first £100,000, and our job was also to make ourselves known to the people in the neuromuscular field.  If you have lab time, if you have research time and you have a choice where you're putting it there is a place you can go to for a myotubular myopathy related grant application, so it's not just that this will come to us out of the blue, people will have done prior work, and our existence makes it worth their while, hopefully, to have done that prior work.  Ana Lisa: That's an amazing story how you've set up this charity and how successful that first application for gene therapy was. I'd love to hear more about that gene therapy and did it get to the clinic and to hear that story from you.  Because I think there are a lot of learnings and it's really important that the first patients who are treated, the first families that are involved, the researchers who start researching in this area, the first treatments lead the way and we learn for all the other treatments for all the other rare conditions that we hope and that together as a community we can share these learnings.  Anne: Yeah. I sometimes describe it a bit like going out into space. When you see a rocket going off look at how many people are behind and the amount of work that's been done, the degree of detail that's managed, and then you go out into space and there are a whole load of unknowns, and you can't account for all of them.  Who knows what's out there in this sphere.  But the amount of preparation, it feels similar to me now, looking back.  We were so idealistic at the beginning.  Our grant to Dr Buj Bello was 2008 and actually it is a really fast time in, the first child was dosed in the gene therapy trial in September 2017.  Ana Lisa: So, we're talking less than 1 years.  Anne: Yeah. And in the meantime obviously as a charity we're also funding other proof of principle research. One of the founding principles of the charity was to have a really excellent peer review process and scientific advisory board so that we wouldn't get carried away with excitement about one lab, one research team, that everything would always come back to peer review and would be looked at coldly, objectively. I don't know how many times I've sat in a scientific advisory board meeting with my fingers crossed hoping that a certain application would get through because it looked wonderful to me, and then the peer review comes back and there are things you just don't know as a patient organisation. So, yes, in those 9 years we were also funding other work.  Ana Lisa: You've just given an interesting perspective on sharing the learnings between the scientists, clinicians, the experts in a particular condition, if you like, and the families, and I'd be really interested to hear your views on what's been learnt about how families and the patient community can also teach the clinical and scientific community.  Anne: So, the first child was dosed in September 2017 and by the World Muscle Society Conference 2 years later in October 2019 the biotech had some fantastic results to show. Children who had been 24-hour ventilated were now ventilator-free, which, unless you know what it's like to have somebody in front of you who's ventilator-dependent, the idea that they could become ventilator-free is just extraordinary.    However, one of the things we've learnt about gene therapy is that we are going out into space so there are extraordinary things to be found, and extraordinary results are possible, as is evidenced here, but there is so much that we don't know once we are dealing with gene therapy. So unfortunately, in May, June and August of 2020, 3 little boys died on the clinical trial. So we have a clinical trial where the most extraordinary results are possible, and the worst results are possible, and both of those things are down to the gene…  What we discovered and what is still being uncovered and discovered is that myotubular myopathy is not just a neuromuscular disorder, it is a disorder of the liver too, and these children didn't die of an immune response, which is what everybody assumes is going to happen in these trials, they died of liver complications.    And one of the things that has come out of that, well, 2 sides to that. Number one is that it is extraordinary that we have found a treatment that makes every single muscle cell in the body pick up the protein that was missing and produce that protein, but also what we've understood is that the knowledge and experience of families and patients is even more vital than we've all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family they would tell you, “Yes, my son has had the odd liver result, yes.”    We could see something that looked like it was not that relevant because it was outside the big picture of the disease, which was about breathing and walking and muscles, but actually there was this thing going on at the same time where the children had liver complications. There were some very serious liver complications but everybody thought that was a minor issue but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing.  Ana Lisa: Yeah, thank you very much for sharing such a moving story and with such powerful lessons for the whole community about how we listen to the expertise that families have about their condition, and also I think the really important point about how we tackle the research funding so that we're including and sharing learnings from the conditions that are initially studied in greater depth, and we hope that many more conditions will be better understood and more treatments found and that actually the learnings from these first gene therapy trials will really help inform future trials, not just for gene therapies but also for many other novel therapies that are being developed.  [Music plays] If you're enjoying what you've heard today, and you'd like to hear some more great tales from the genomics coalface, why don't you join us on The Road to Genome podcast. Where our host Helen Bethel, chats to the professionals, experts and patients involved in genomics today. In our new series, Helen talks to a fantastic array of guests, including the rapping consultant, clinical geneticist, Professor Julian Barwell, about Fragile X syndrome, cancer genomics and a holistic approach to his practice - a genuine mic-drop of an interview. The Road to Genome is available wherever you get your podcasts. [Music plays] Ana Lisa: Carlo, I would really like to come to you about some of the initiatives that are happening in the UK, and particularly it would be really interesting to hear about the UK Platform for Nucleic Acid Therapies as a sort of shining example of trying to do something at a national scale across potentially many different rare conditions.    Carlo: Thanks, Ana-Lisa. Thanks very much, Anne, for sharing your fantastic story. I mean, I just want to iterate that as clinician scientists we do constantly learn from experiences and constantly learn from you, from the patient community, and this is absolutely valuable to push the boundary. And I really liked your vision of a rocket being launched in space and I would imagine that this is a similar situation here. So, we are facing a major challenge. So, there is over 7,000 rare diseases in the world and with improvements of genetic diagnosis this is only increasing. So, in a way rare diseases is the ultimate frontier of personalised medicine and this poses incredible challenges.   So, you mentioned the bottom-up approach and the top-down approach and in a way, both are absolutely necessary. So your story is a fantastic story but also makes me think of all the other families where they don't share perhaps the same spirit, you know, they are in areas of the world that are not as well connected or informed, where patient community simply cannot be ‘nucleated', let's say, around the family. So, there is definitely an issue of inclusivity and fair access.    So, what we're trying to do at UPNAT, which is the UK Platform for Nucleic Acid Therapy, is to try to streamline the development both at preclinical and clinical level of nucleic acid therapies. So, we'll start with antisense oligonucleotides just because those are the molecules of the class of drugs that are most ‘mature', let's say, in clinic. So, there are several antisense oligonucleotides already approved in the clinic, we know that they are reasonably safe, we understand them quite well, but of course the aspiration is to then progress into other forms of gene therapy, including gene editing approaches, for example.   And one of the activities that I'm involved, together with Professor Muntoni, is to try to streamline the regulatory process of such therapies and in particular curate a registry of, for example, side effects associated with nucleic acid therapy in the real world, and you would be surprised that this is something that is not yet available.  And the point is exactly that, it's trying to understand and learn from previous mistakes perhaps or previous experiences more in general.    And this is very much in synergy with other activities in the UK in the rare disease domain.  I'm thinking of the Rare Disease Therapy Launchpad, I'm thinking of the Oxford Harrington Centre, I am thinking of the recently funded MRC CoRE in Therapeutic Genomics. These are all very synergistic. Our point is we want to try to amplify the voice of the patient, the voice of the clinicians working on rare disease, and we want to systematise. Because of course one of the risks of rare disease therapies is the fragmentation that we do all these things in isolation. And I would argue that the UK at the moment leveraging on the relatively flexible and independent regulatory agencies, such as the MHRA, on the enormous amount of genetics data available through Genomics England, and of course the centralised healthcare system, such as the NHS, is really probably the best place in the world to do research in the rare disease area, and probably I'm allowed to say it because I'm a non-UK native.       Ana Lisa: Thank you, that's a brilliant perspective, Carlo, and across all the different therapeutic initiatives that you're involved with. And, Carlo, presumably - we're all hoping - these different initiatives will actually lead to ultimately a bigger scaling as more and more novel therapies that target both our RNA and DNA and actually are working, I guess further upstream in the pathway.    So classically in the past it's been necessary to work out all the underlying biology, find a druggable target somewhere in that pathway and then get a larger enough clinical trial, which can be nearly impossible with many of the rare and ultra-rare conditions or even, as you've said, the sub-setting down of more common condition into rarer subtypes that perhaps can be treated in different ways.  And with the many new different treatments on the horizon, ASO therapies, as you've said, is a place that's rapidly expanding, and also crisper gene editing. I'd be really interested to hear your reflections on how this might scale and also how it might extend to other new treatments.  Carlo: Yeah, that's exactly the right word, ‘scaling up'. I mean, there will be of course very unique challenges to every single rare disease but I would argue that with genetic therapies, such as ASOs or crisper gene editing, the amount of functional work that you need to do in a lab to prove yourself and the scientific community that this is the right approach to go for can be certainly very important but can be less just because you're addressing very directly because of the disease.    And then there are commonalities to all these approaches and possibly, you know, a platform approach type of regulatory approval might serve in that regard. You know, if you are using the same chemistry of these antisense oligonucleotides and, you know, similar doses, in a way the amount of work that you need to produce to again make sure that the approach is indeed a safe approach and an effective approach might be also reduced.    I would say that there are also challenges on other aspects of course, as you were saying, Ana-Lisa. Certainly the typical or standard randomised placebo control trial that is the standard and ultimate trial that we use in a clinical setting to prove that a molecule is better than a placebo is many times in the context of rare diseases simply not possible, so we need to think of other ways to prove that a drug is safe and is effective.   This is something that we all collectively as a scientific community are trying to address, and the alliance with the regulatory agencies, such as the MHRA, and you said that you have found your interaction with the MHRA very positive, and I can tell you exactly the same. So we are all trying to go for the same goal, effectively, so trying to find a way to systematise, platformise these sort of approaches. And I guess starting with antisense oligonucleotides is really the right place to go because it's a class of drugs that we have known for a long time, and we know it can work.  Ana Lisa: Meriel, can you tell us a little about the National Genomic Research Library at Genomics England and how this could link with initiatives to find many more patients as new treatments become available for rare and ultra-rare conditions?  Meriel: Yes, I think what's wonderful now is actually that what we're really trying to do is give everybody the opportunity to have their rare condition specifically diagnosed at the molecular level, and the way in which that is being done is by offering whole genome sequencing in the NHS currently in England but to all patients with rare diseases.    And so, it's about trying to establish their diagnosis. And as well as that, even if the diagnosis isn't definitely made at the first pass when the clinical scientists look at the data, because the whole genome has been sequenced, actually all that information about their genome, if they consent, can then be put into the National Genomics Research Library.  And that is a fantastic resource for national and international researchers who get approved to work in this trusted research environment to make new disease gene discoveries and identify these diagnoses for patients.  What's also offered by Genomics England as well is when the National Genomics Library data results in a new publication, the discovery of a new gene or perhaps a new molecular mechanism that causes a disease we already know about, that feeds back into the diagnostic discovery pathway within Genomics England back onto the diagnostic side of all the data.    So, patients who may have had genetic testing previously using whole genome sequencing where they've, if you like, had their sequencing done before the diagnosis was sort of known about, will also be picked up. And so, what this is really doing is trying to kind of give this really equal platform for everybody having testing to all have the same opportunity to have their diagnosis made, either on the diagnostic side or with research.  Ana Lisa: So, sort of on a cohort-wide scale as new discoveries are made and published you can go back and find those patients that may actually have that diagnosis and get it back to them, which is brilliant.  Meriel: Exactly. And this speeds up the whole process of getting these diagnoses back to people. So on a regular basis in the NHS, we will get feedback from the Diagnostic Discovery Pathway about “Here's some patients who you requested whole genome sequencing from a number of years ago and actually now we think we know what the particular molecular condition is.”  And so, it's key of course for our patients with rare conditions to make that molecular diagnosis because then we're able to have them identified for our colleagues who are doing this ground-breaking research trying to bring therapies for these rare conditions.  Ana Lisa: Thank you. And I hope that, as currently, if a novel genetic mechanism, as you've just described, is identified that could explain a rare condition that those patients can be found and they can receive that diagnosis, even many years later, and hopefully as novel treatments become available and say there's a chance to individualise ASO therapies, for example, to start with, that one could also go and look for patients with particular variants that could be amenable potentially to that treatment. And that's really sort of exciting that one could look for those patients across England, irrespective of which clinic they're under, which specialist they're under, and I think that could be really powerful as new treatments develop. I suppose, Meriel, if somebody comes to see you now in clinic are things different?  Meriel: Well, I think one of the things for me when patients come to clinic now is we might have an idea about what we think their condition is, maybe even we think it's a specific gene. And we can offer whole genome sequencing and so it's not just the way we used to do things before by looking just at the coding regions of the gene, we can find more unusual ways in which the gene can be perturbed using whole genome sequencing.  But let's say we don't make the diagnosis. I encourage my patients, if they're comfortable with it, to join the National Genomics Research Library, because really it's been incredibly productive seeing the new genetic discoveries that are coming out of that, but as well I say to them, even if we don't get the diagnosis the first time round when we look at the data, actually this is a constant cycle of relooking at their data, either if they're in the NGRL or as well on the Diagnostic Discovery Pathway side of the service that's run by Genomics England. So yeah, I feel like it's a very big difference; they don't have to keep coming every year and saying, “Is there a new test?” because actually they've had an excellent test, it's just developing our skills to really analyse it well.  Ana Lisa: Yes, and our knowledge, the technology and the skills keep evolving, certainly.  And I think one of the things that I'm sort of hearing from this conversation is that balance of hope and realism, Carlo we were talking about earlier how you need all the pieces of the puzzle to be lined up - so the regulatory agency, the clinicians, all the preclinical work has to have been done, monitoring afterwards for side effects - every piece of the puzzle has to be lined up for a new treatment to make it to a patient.    And, Anne, I'd like to come back to you because we've talked about this before, how one balances these messages of optimism and hope which are needed for bringing everybody together as a community to crack some of these very difficult challenges highlighted by treatments for rare and ultra-rare conditions and at the same time the need for realism, a balance conversation.  Anne: Yeah, that was one of our big learnings through the gene therapy trial and other trials we've had in the condition. As a rare disease charity, you do everything. You know, my title is CEO, but I tell people that's Chief Everything Officer because there's only a few of you and you do everything. So, you go and you lead the London Hope Walk and you also are a layperson on the Scientific Advisory Board and you also send out the emails about grants... And so, you could easily as a small rare disease charity conflate different communication messages because you're in a certain mode.  And so we have been from the early days in the mode of raising hope for people to say, “Look, we can make a difference as a patient community, we could raise funds, we might be able to move things forward, you've got the power to make a difference if you want to.” That's one set of hope.  And it's not dreamlike hope, we're linked to the reality of there are great breakthroughs.  So, you know, in the world of spinal muscular atrophy these clinical trials have led somewhere very quickly, so we're not selling false hope, we're talking about the difference we can make.    But then as soon as you flip into “There's a clinical trial being run” that's a completely different type of communication and you cannot conflate that message with the previous message.  And we always say to everybody, “We're your team, we're a family, we're a team, we all help each other.  When you are considering joining a clinical trial your team is the clinical trial team.    The other team does other things for you but the people you need to work with and ask hard questions of and listen hard to, that's your clinical trial team led by the principal investigator because then you're in that with them. And, you know, the reality of the fact that many, many clinical trials don't work as we wish they would be and the decision you make for your child, your baby, your little one, to join a clinical trial… because that's what it comes down to in our disease, has to be made with that team, not the team that's selling you a fundraising event. It's worth reminding rare disease patient organisations we're wearing different hats and the hope and the realism are different tracks you have to go down.    But at the same time as being realistic you also have to keep remembering that there is still grounds for hope, we are moving forward. And 21 years ago, when Tom was born the idea that you would be able to get all of the muscles in the body to switch back on – putting it in lay terms – seemed like a bit dream. Well, that is what has happened in the gene therapy clinical trial, we just have to now make it safer and understand more about what we're dealing with. So, the 2 things, the hope and the realism, do exist side by side.  Ana Lisa: I think that perfectly encapsulates a lot of the messages around rare disease therapies where there's such hope that novel treatments will really target directly the DNA or RNA to potentially correct the problem across many different rare conditions and therefore actually making treatments one day suddenly available to a much, much bigger population of people with rare conditions than we could've dreamt of 20 years ago or perhaps now, and at the same time this massive need to work cooperatively to all make this as fair, as equitable. Not everybody is going to have the opportunity to fundraise massively to be an expert about their condition, and the importance of sharing these learnings and also really, really listening to the patient community and really, as Carlo was saying, keeping track of side effects, having registries/databases to share these is going to be incredibly important.  [Music plays]  Ana Lisa:  Anne, can you tell us a little about your reflections on equity from the patient community perspective?  Anne: Well I mentioned serendipity early and one of the aspects of serendipity that played into our favour for setting up the Myotubular Trust was that by hook or by crook Wendy Hughes, who set up the charity with me, and I were both able to devote time at that period of our lives to setting up a charity. When my husband, Andrew, and I were told that Tom would more than likely die before his first birthday, one of the decisions we made as a family was that he would never not be with a parent, we would always have someone around, and that kind of meant someone had to give up a full-time job and that was me.  We thought, “If Tom has a few scarce months on the planet, we'll be with him.” And then when Tom lived to be nearly 4, as a family we got used to living on one salary and we were very lucky that we could pay the mortgage that way and run our family that way and eventually that meant I had the time to run the charity.    That doesn't happen that easily, that's a tall order, particularly when you have somebody in the family who has such high needs. And one of the things that I have often thought about is that in the rare disease space we could do with a different funding model for rare disease charities, we could, in an ideal world I have this nirvana that I imagine where there's a fund that you can apply to that is contributed to by the people who make profits out of finding rare disease cures - so the pharmaceutical companies and the biotechs - and there's a fund that they contribute to and that if you have a rare disease and you are willing to set up an organisation that supports families, that raises research funds, that provides a way of hearing the patient voice, then you could apply to that for running cost funds and then you'd be able to run this charity. And then you wouldn't have to rely on whether you live in an area where people will raise money for you or…  We were very lucky that we came across a few great benefactors who would give us money for running the charity, which is actually how we fund it.    All the research money we raise goes 100% into research, not a penny of it goes towards running costs because we have serendipitously found people who will be benefactors for the charity, but we're relying on a lot of good luck for that kind of model to work. And when you look at how much profit is made from developing rare disease treatments and cures – which is fine because that's what puts the passion and that gets people working on it – then why not have an advance fund to run rare disease charities? One of my nirvana dreams.  Ana Lisa: It's good to dream. Indeed, my hope is that there will be some amazing shining examples that lead the way that open doors, make things possible, prove that something can work and how and that then that will enable many other treatments for many additional rare conditions to be added in so that if you've learnt how this particular treatment modality works for this rare condition and there was funding behind it and everything else that's needed that then you can, the learning from that, I'm going to use the word ‘tweak', which sounds minor and could be very major but actually the concept that you can then tweak all those learnings and findings so that that same type of treatment modality could be adapted to treat somebody else with a different rare condition in a different location would be absolutely incredible and really powerful, given that if something like 85% of rare conditions affect less than one in a million people it's not going to be feasible to use the same strategies that have been used in the past for very common conditions.    One of the other big barriers is the cost of developing treatment for ultra-rare conditions.  Where it's a small number of patients that you have and therefore all the challenges that come with monitoring, checking for efficacy, monitoring safety and ultimately funding the challenges are much greater, however if some of these treatment modalities are also going to be used to treat common conditions it might be that actually there's a lot more cross-talk between the nano-rare, ultra-rare, rare and common conditions and that we can share a lot of that learning. I'd love to hear from each of you where you hope we will be for rare disease and rare therapies.  Carlo: Well my dream is that in 5 to 10 years' time an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested, and at that exact time the day of the diagnosis becomes also a day of hope in a way where immediately the researcher, the centre, genetics lab, flags that there are the specific mutations, we know exactly which is the best genetic therapy to go after, antisense oligonucleotides as opposed to CRISPR editing, and a path forward, both at the preclinical and clinical level, to demonstrate and to cure these patients eventually is already laid out in front of the patient.  So, transforming the day of their diagnosis as a day of hope, this is my dream with the next ten years.  Ana Lisa: Thank you, that's a wonderful dream. Meriel, can I come to you?  Meriel: Yes, I think I just want to echo Carlo.  We've had great developments and progress with getting whole genome sequencing into the NHS for testing but what we really need is for it to be fast and efficient and getting those diagnoses established quickly. And we have had that set up now and we're really getting there in terms of speed, but then what we need is exactly what's the next step and actually structure like UPNAT that are developing these processes that we can then say to the patient, “And from there, now that we've established your diagnosis, this is what we have options to offer.”  Ana Lisa: Brilliant. And presumably that if the diagnosis isn't achieved now there is a hope that it will be achieved in the future as well. Anne...  Anne: Well, stepping one hundred per cent into the patient's shoes rather than the scientific side that we don't so much influence....  stepping in the patient's shoes, in 5 years' time I would absolutely love it if we were in a situation where all the parties that have come to the table looking at a therapy or in the earlier research genuinely want to bring the patient voice into the room. As Carlo talked about, there's even going to be more and more and more of these rare diseases, then those voices, those few people who have experience of it, they may be able to shed light on something. Maybe even sometimes don't even know it's a fact that they know but that were brought to the table as passionately as everything else is brought to the table.  [Music plays]  Ana Lisa: We'll wrap up there. Thank you so much to our guests, Anne Lennox, Carlo Rinaldi and Meriel McEntagart, for joining me today as we discuss the collaborative power of working together and look to the future of rare therapies that could have the potential to unlock treatments for many rare conditions. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I've been your host, Ana-Lisa Tavares. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.  

Michael welcomes Sandy Rolfe, Chair of the WEDI Genomics Workgroup and Clinical Lead for the InterQual Molecular Diagnostics and Durable Medical Equipment at Optum. The two discuss the ever evolving state of Genomics research, data privacy and security, and how data interoperability and standards can aid in care and patient satisfaction. WEDI members are invited to attend a special Genomics workgroup event, Exploring Genomic Data Exchange: A Deep Dive into FHIR Integration and Interoperability, Feb 27 on Zoom, exclusive for WEDI members. Visit www.wedi.org to sign up.

Regional Clinical Lead for Strategy and Development of health services in the Mid West, Dr Hennessey, joins Gillian on the show Hosted on Acast. See acast.com/privacy for more information.

Richard Hales has spent the last 22 years fixing Royal Marines at the Command Training Centre Royal Marines (CTCRM) Lympstone in the UK and is the Clinical Lead within their bespoke Exercise Rehabilitation Centre. So he knows a thing or two about the role of physiotherapy in a pressurised physical environment. The team delve into the role of a physiotherapist in both prevention and recovery; explains how data drives much of the research, why old-school physio techniques are questionable and whether biomechanics make a difference in causing chronic injury.Hales graduated with a Sports Science degree from Liverpool University in 1992 before qualifying as a Chartered Physiotherapist from Bath University in 1996.Having chosen to specialise in musculoskeletal rehabilitation his roles have included six years as Physio with Exeter Chiefs Rugby Union Club, and clinical co-ordinator for Amputee rehabilitation within ‘Adventure Rehab', as well as Out-Patient work in both the UK and New Zealand before joining the military.He has just written a book about his time working with the Royal Marines entitled The NOD Fixer which is due out in Easter 2025.Join DiscourseIf you fancy a bit of the coaching, sports science and sports news conversations with our amazing members, consider a small donation to become a Patron of the site, and get access to our Discourse community, where you can join like-minded fans and sports enthusiasts to keep the conversation going. Get bonus content on Patreon Hosted on Acast. See acast.com/privacy for more information.

In this week's episode, Han is joined by Zuzanna Gajowiec. Zuzanna is a Clinical Psychologist, Family Therapist, and Ireland's first Certified Eating Disorder Specialist and Consultant (CEDS-C). With over a decade of experience, Zuzanna is dedicated to supporting individuals and families on their journey to recovery, focusing on physical healing, body image, and family connections.As the IAEDP Chapter Chair of Ireland and Clinical Lead at a Residential Eating Disorder Treatment Centre, Zuzanna also teaches, consults, and supervises other therapists, sharing her expertise to advance the understanding of eating disorders.This week, we discuss:The science behind GLP-1 and how they work in the body.The impact of GLP-1s being presented as a safe, miracle drug.The difference in dosage and use for diabetes and weight loss, and the lack of research.The side effects of misuse of GLP-1 medications.How GLP-1 medications can implicate ED treatment and impact recovery.The importance of health care professionals understanding GLP-1 medications.The attraction of quick fixes as opposed to difficult therapy and how we navigate this.Zuzanna mentioned a few resources in the podcast, and you can find them here:GLP-1 research in ED populationsRagen Chastain's narrative on GLP-1 medicationsRagen Chastain's Substack To find out more about Zuzanna, you can connect with her in the following places:Instagram - @supported_familiesWebsite - https://supportedfamilies.ie/LinkedIn – Zuzanna GajowiecPlease note that this podcast explores topics some individuals may find difficult to hear and should not be used as a replacement for professional advice. If you need further support after this podcast, please consider talking to someone you trust. You may also wish to reach out to your GP or mental health professional.We've included a list of additional support options in case you need them:Samaritans are here for whatever you are going through. You can call free any time, from any phone, on 116 123.FirstSteps Eating Disorders is an eating disorders charity for children and their families, young people, and adults affected by eating difficulties and disorders. You can call them on or email info@firststepsed.co.uk.Beat Eating Disorders is an eating disorder charity offering support for those with or supporting someone with an eating disorder. You can call their helpline for free on 0808 801 0677 (England), 0808 801 0432 (Scotland), 0808 801 0433 (Wales), 0808 801 0434 (Northern Ireland).

In this episode, one of our menopause private coaches, Laura sits down with Lydia, an inspiring woman who's 57 years young and proving that it's never too late to transform your health and rediscover your confidence. Lydia works as a Clinical Lead in the NHS, balancing a high-pressure job, family life, and all the challenges […]

Catherine Motherway, Clinical Lead for Organ Donation and Transplant Ireland in the HSE,

The National Institute for Health and Care Excellence in the UK looks set to reduce the number of people to be offered what's known as the ‘King Kong' of weight loss, Mounjaro. They are now going to offer the drug only to those with the highest clinical needs. Dr. Michael Crotty, the Irish College of GP's Clinical Lead on Obesity tells us more.

In this explainer episode, we've asked Meriel McEntagart, Clinical Geneticist in the NHS and Clinical Lead for Rare Disease Technologies at Genomics England, to explain how genetic conditions can be inherited, and other ways they may arise. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you've got any questions, or have any other topics you'd like us to explain, feel free to contact us on info@genomicsengland.co.uk. To learn more about X-linked inheritance, as mentioned in the episode, tune in to our explainer episode, how does X-linked inheritance work? You can download the transcript or read it below. Florence: Are genetic conditions always inherited from parents? I'm joined by Meriel McEntagart, clinical geneticist for the NHS to find out more. So, Meriel, first things first. How can a genetic change cause a condition?   Meriel: We have about 20,000 genes. That's the estimate and they are the code or blueprint for how to grow and develop a human being. And, if you think about a code, you can have a mistake in a code or a variant in a code. And if that happens, such as one genetic letter being changed for another, the result can be that the code doesn't give the correct instructions about how to grow and develop that human being. There are lots of different ways in which those changes can happen.  Florence: And how can we inherit conditions from our parents?   Meriel: Well, for the most part, like I mentioned, we've got 20,000 pairs of genes and we get one of each pair from our mother and our father. And so, for lots of genetic conditions, they follow a pattern of inheritance where one copy of that pair of genes has got the variant or spelling mistake in it, which causes the condition.  So just having a single mistake in that pair of genes is enough to cause you to develop the symptoms of the condition. Other conditions show where you only develop the condition if both copies of the pair, the one you get from your mother and the one you get from your father have got a variant or a spelling mistake in the gene.  So, you actually don't have a working copy of that gene. There are other patterns of inheritance as well. And so, we talk about X-linked inheritance. That can arise because women have what we call two X chromosomes; men only have one X chromosome.  Florence: If you want to learn more about X-linked Inheritance, you can check out our previous podcast. How does X-linked inheritance work? So then do parents who have a condition always pass it on to their children?  Meriel: So, this is again, where we think about some of those patterns of inheritance that I've just mentioned. If somebody has a condition, for example, a dominant condition, they will have that variant or genetic change that's causing their condition in one of their pair of genes. So then it's 50:50 when they have a child, whether they pass on the gene that's carrying that variant or not, because the child will be getting the other copy of that pair from their partner.  If they do inherit that copy with the variant in it, then they will develop the symptoms of the condition in most cases. In some situations, however, a parent can have a genetic condition. So, they develop symptoms of the condition, and as I've mentioned, it's 50:50, whether it gets passed onto the child, so the child could actually inherit that genetic variant, but potentially not show signs of the condition. And this is what we call ‘reduced penetrance'. This means you can carry a genetic variant and probably some other event has to take place to cause you to develop symptoms.  So that might be that there's other genetic factors that you inherit that trigger you to develop symptoms or there might be an illness or something that you experience that brings out the expression of that gene. So that's quite an important, consideration when we're looking at genetic variants and whether somebody will develop symptoms.  Florence: And finally, how do we develop conditions that don't come from our parents?  Meriel: Well, I suppose the main explanation for that is what we call a de novo genetic event. So that can arise when we are conceived. So for example, genes get copied to be put into the sperm or our genes get copied to be put into the egg. And in that process of making the sperm and the egg, a spelling mistake or mutation can arise in the DNA and then that sperm or that egg, whichever one has it, takes that forward into making the baby. And then the baby from that point will have that genetic variant in every single cell in their body. So it hasn't come from the parents, so it's not inherited but it still is a genetic condition. This is something that now that we're able to do whole genome sequencing, we are finding is a more common explanation for developmental disorders or conditions in children than we previously appreciated. And quite a lot of conditions where the child has congenital abnormalities when they're born, like a congenital heart problem with some global development delay or difficulties or some other sort of problem, when we do their whole genome sequencing, we find that they have a de novo mutation in an important developmental gene.  There are also some more unusual ways in which a genetic condition can arise for the first time in the family. The first example I might give is, the condition, Huntington's disease. Huntington's disease is a neurodegenerative condition that causes a movement disorder, often starting in adult life. And sometimes people will know that it's in their family. However, sometimes it can arise in somebody and there's no history of it in the family at all.  Huntington's disease is what we call a triplet repeat condition. This is where, in our DNA sometimes we have little strings of letters that are repeating after each other. So, usually we'd have 25 repeats or less. This can slip up on transmission from a parent to the child, so it can increase in size and if it slips up into the range of 40 repeats or more, then that person will develop symptoms of the condition.  Another example I thought that might be worth mentioning is what we call imprinting. When we inherit our genes from our parents, for some genes, it actually matters whether the gene copy has come from your mum or from your dad, and it will have an imprint or a mark on it that says, this is the maternal copy, this is the paternal copy.  The reason that imprint is there is that it may potentially switch off that gene and say, this shouldn't be expressed in the baby. And if this doesn't work properly, you can get some conditions like for example, Prader-Willi Syndrome. This is where a child has developmental delay and maybe a very increased appetite. And it's because the differential gene expression hasn't worked. Florence: That was Meriel McEntagart, explaining whether genetic conditions are always inherited. If you would like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.

In this episode, we explore findings from a groundbreaking study recently published in Nature which revealed potential targets for bowel cancer prevention and treatment. The study provides the most detailed understanding yet of bowel cancer's genetic makeup. The research, which used data from the 100,000 Genomes Project identified over 250 genes that play a crucial role in the condition, driver genes and potential drug targets. Our guests discuss the potential impact of these findings on patient outcomes, screening for bowel cancer, and future prevention strategies. Helen White, Participant Panel Vice-Chair for Cancer at Genomics England is joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University. "The people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldn't benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what we're seeking to realise now. But, you know, it's not a given when we treat people in the clinic so we're very, very grateful to those individuals." You can read more about the study in our colorectal cancer blog and our study findings news story. You can download the transcript or read it below. Helen: Welcome to Behind the Genes. Ian: One of the great hopes is that some of these new genes that we've found could be useful in preventing cancer and it doesn't necessarily matter that they're rare, even if they're only 1% of cancers, by using those and changing those in the normal individual before they have had cancer then we may be able to reduce that risk. So, there are lots of potential new targets for prevention that are coming through.  My name is Helen White and I'm the Participant Panel Vice-Chair for Cancer at Genomics England. Today I'm delighted to be joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University.   Today we will be discussing a pioneering colorectal cancer study which using data from the 100,000 Genomes Project has uncovered new insights that could transform diagnosis and treatment for patients with bowel cancer. If you enjoyed today's episode we would love your support, please like, share and rate us on wherever you listen to your podcast.  Thank you for joining me today. We're going to be discussing the findings from a landmark study that has been published in nature. This study used data generously donated by people with bowel cancer who took part in the 100,000 Genomes Project giving us the most detailed look yet at the genetic makeup of colorectal cancer better known as bowel cancer. But before we get into that let's start by hearing from my guests. Could each of you please introduce yourselves.  Ian: I'm Ian Tomlinson, I work at the University of Oxford and most of my work is research into bowel cancer, it's genetic causes, the genes that are involved in actually causing the cancer to grow which may be different from genetic causes and also the use of that data to help patients whether guiding future treatments or potentially helping to prevent bowel cancer which would obviously be our optimum strategy to have the biggest impact on the disease and its incidents.   Claire: So, I'm Claire Coughlan, I'm the clinical lead for Bowel Cancer UK and my remit at the charity is to ensure that everything we do is clinically relevant and that we're providing services that meet the needs of those affected by bowel cancer and the educational needs of those health professionals that work with people affected by bowel cancer. I'm also a nurse consultant in colorectal cancer at Lewisham and Greenwich NHS Trust and I lead an urgent referral service there and also work with patients with late effects of bowel cancer.  David: I'm David Church, I'm a medical oncologist and Cancer Research UK advanced clinician scientist at the University of Oxford. I treat bowel cancer clinically and do research on bowel cancer and womb cancer including a lot of research using samples and data from Genomics England data service we're discussing today of course.  Helen: Great, thank you. Now let's turn to Claire to learn more about bowel cancer. Claire, can you share with us how common it is, how treatable it is and if there are any trends in terms of which groups of people are affected?  Claire: Of course, bowel cancer is a relatively common cancer, there are about 46,000 people each year in the UK diagnosed with bowel cancer so that is quite a large number. The thing that really drives us forward in bowel cancer is that the earlier stage you're diagnosed at the greater chance of survival. So, the figures for that are quite stark, we stage bowel cancer through stage one to 4 with one being the earliest stage and 4 being the most advanced.   If you are diagnosed with bowel cancer at stage one you have a 9 in 10 chance of being alive and well 5 years after your diagnosis of bowel cancer. And if you're diagnosed at the other end of the spectrum at stage 4 that drops to a 1 in 10 and should people survive after a diagnosis of stage 4, which more people than before do they will have had a lot of treatment for their bowel cancer so the burden of the treatment will also be with them after that. So, it's really important that we diagnose at the earliest possible stage which is why studies such as the one we're going to talk about today are so important.   We have noticed that there has been a slight increase in being diagnosed at a younger age. That said the latest statistic is 2,600 people were diagnosed under the age 50 in the UK last year so it's still a disease of older people, you still have a greater chance of getting bowel cancer as you get older but it's really, really important that we're aware that you can still get bowel cancer as a younger person.   Probably one of the most exciting things that has happened for bowel cancer of recent years is our bowel cancer screening programme and the age for that now has been brought down to 50, we're not quite there all over the country, but in the UK that is the aim that everyone will be screened for bowel cancer at the age of 50. So, yes it's a common disease and staging an early detection is vital. Helen: That's lovely Claire, thank you very much for that. David, turning to you could you please explain to us how bowel cancer typically develops? David: Yes, so we know compared with many cancer types quite a lot about how bowel cancer develops because the bowel is accessible to collect samples by a technique called endoscopy which is putting a camera into the bowel from which you can sample tumours or lumps. And so from genetic research done in the last 10 years we know that, or we've known for many years actually, for much longer, that cancer is a genetic disease, it's a disease caused by alterations in genes and particularly genes that control whether the cells in our bowel grow normally and die normally as they should do. And collectively when there are alterations in genes that regulate those processes you can have a cell or collection of cells which are able to grow without restraint and don't die when they should do which are some of the hallmarks of a cancer and they also require the ability to spread elsewhere in the body which is what kills people with cancer including bowel cancer. We know from research done in the last 10 to 15 years that some of the alterations in genes that can cause bowel cancer in combination occur very early in our life, even in the first and second decade of life, but don't cause cancer. The earliest detectable abnormality is typically a polyp which is a tumour, a lump within the bowel which is detectable and if removed is almost certainly cured by removal alone but if it's not detected then as that grows and acquires more alterations in genes then it can become a cancer and cancers develop the ability to invade the bowel wall, to spread to what we call lymph nodes or glands nearby and also to spread further afield, most commonly to the liver or to the lungs.   And for most people whom bowel cancer has spread to the liver or to the lungs or elsewhere unfortunately we're not able to cure their disease which as Claire has said is why there is such an importance in detecting cancers and pre-cancers as we call them so that the tumours are not actually cancerous but come before bowel cancer as early as possible.  Helen: Thank you David. Moving on to the study, Ian perhaps you can take this, in the study that you carried out my understanding is that the whole genome sequencing was used to investigate the genetic changes that lead to the development and growth of bowel cancer. And for this participants with bowel cancer in the 100,000 Genomes Project donated both a blood sample and a tumour sample while those with rare conditions only provided a blood sample, can you explain why that is?  Ian: As you said the study really looked at 2 quite separate arms albeit with a little bit of overlap as we'll see. So, one very important aim was to look at individuals, both children and adults, who had medical problems or other conditions that were unexplained but which had some features that suggested that they weren't necessarily inherited but there may be some variation in their genes that had caused them, and roughly half of the programme was dedicated to that.   Within that there was a small number of people who had a strong family history of bowel cancer or who had large numbers of polyps in the bowel and they were analysed in a separate part of the project from what we're mostly discussing. Within the cancer arm there was a collection really throughout England of patients who had most of the common types of cancer and a few with less common cancers.   And because when we're looking at genetic and related changes in cancers we need to make sure that those changes have actually occurred in the cancer as it started growing from its earliest stages with a small number of cells in the body that were slightly abnormal and then progressing. We need to look at what genetic variation the patient has in all the cells of their body. We don't want to look at patients and say that looks an interesting change, we may be able to use that if it's present in all of the normal cells in that patient's system.   We want to make sure the change is specific to the cancer itself and therefore we have to sequence both a sample probably taken from blood and a sample taken from the actual cancer. And in a way we subtract out the changes in the blood to identify the changes that have actually occurred in the cancer itself.  Helen: That's a very helpful explanation. Does this research show that there is a role for whole genome sequencing in clinical care?  Ian: I think my own view is it is all a question of cost. I think the advantages it provides it can assess multiple types of genetic change at once. It is relatively consistent across each cancer's genome between cancers, even between centres mean that it is the method of choice. There are undoubtedly developments that will happen in the future, maybe being able to sequence longer stretches of DNA in one go that will help the analysis.   And some of the computational methods are likely to develop to identify some of the slightly difficult to identify genetic changes but it ought to be the standard of choice. There are issues and potential difficulties in collecting the high-quality samples that have been needed from pathology laboratory and that will be difficult going forward with current budges and there are lots of challenges but ultimately it in some form has to be the method of choice. What wasn't done is to look at other molecule tests or essays, looking at RNA wasn't really done on a big scale as well as DNA and other changes to DNA apart from the genetic changes were not looked at.   So, there are certainly ways it could be improved if you had limitless money but I think the project, 100,000 Genomes has shown the whole genomes are. They have a lot of advantages and ultimately probably will be adopted by the NHS and similar organisations.  Helen: David, could you now tell us about the findings of this pioneering study and what impact these findings might have on people with bowel cancer in the future?  David: So, this is the largest study to date to analyse the entire genome of bowel cancer by some margin and the fact that we've done whole genome sequencing and in so many people it has really given us an unprecedented ability to identify the genetic alterations that drive bowel cancer. And within bowel cancer we've known for some time it is not a homogeneous entity that bowel cancer is not all created equal, that there are sub-groups of bowel cancer and we have been able to refine those over previous efforts. And I guess if you were to ask what the biggest take home for me from the study is it's just the complexity of the disease.   So, as we've mentioned we know that cancer is a genetic disease, that it's driven by genetic alterations, alterations in genes which regulate the growth of cells or the death of cells or the spread of cells. And we've known for many years that there is a modest number of genes which are commonly malfunctioning in bowel cancer and they would be in the tens to dozens really. But with this work we've hugely extended our understanding of the genes that drive bowel cancer and in fact we've discovered nearly 250 genes which are altered in bowel cancer and appear to drive the growth of the cancer.   Now we know that not all of those will be validated and by that I mean that there are associations that we find at the moment, not all of which will be biologically relevant but interpreted in the data we know a large number that are previously undiscovered are or we can be fairly confident of that. And one of the take homes from that is that many of these are only altered in a small fraction of bowel cancers.   So, rather than being perhaps half of bowel cancers or a third of bowel cancers there are a good number of genes, a very substantial number of genes, which are altered in say 3 to even 1% of bowel cancers. And if we think about how we go about targeting those and perhaps we'll come onto treatment later that poses really challenges for how we work and we would think about treating patients with bowel cancer who have those particular alterations in their cancers.  Helen: Thank you David, yes we'll come onto treatment shortly, but I think Claire has a question for you.   Claire: Yes, thank you. For me as somebody who works in this every day this is such an exciting and interesting study, particularly in light of what we said earlier about early detection and how critically important that is for improving outcomes in people with bowel cancer. So, in your view do you think this research could help shape future screening programmes or prevention strategies?  David: That's a great question, I suppose in terms of screening at the moment the majority of screening is done in the UK at least by testing for blood in the stool which is relatively non-specific so I'm not sure that that would be directly impacted by this research. But one area of early cancer detection that is perhaps more relevant is quite a lot of work including from Oxford actually in recent years looking at blood tests. So, testing blood samples for early detection of cancer whereby you can test for genetic alterations, fragments of DNA that have alterations from the bowel cancer or any cancer that circulates in the blood and that tends to rely on a small number of common alterations.   And with this data I could see that we might be able to refine those tests and in so doing improve our early detection of cancer but that would need quite some work before we could actually say look that had real potential I think. And in terms of prevention there are, I think Ian may want to come in on this, one or 2 sub-groups which you might think that you could try to prevent but of course that needs a lot of extra work really.   But I think we have some clues of the biology of bowel cancer and particularly some of the sub-groups where you might think well this drug would work better in terms of preventing that sub-group or that sub-group but that will need to be the subject of future study.  Helen: Ian, did you want to come in on that at all?  Ian: So, at the moment prevention is a fairly new way of helping to reduce the number of people with bowel cancer at the level of the whole population which is what we have in the UK above a certain age group as we heard from Claire earlier. The methods used, again as we heard, are screening for occult blood in the stool and then colonoscopy to identify either hopefully early cancers or polyps and remove those. But when we think about the methods that we use for preventing other diseases then normally where they're successful using a more easily delivered and I have to say less expensive method.   So, high blood pressure is treated to reduce the risk of cardiovascular disease and there are other diseases where those what you might call molecularly-based prevented strategies are coming in. We really lack that for bowel cancer in particular, it does happen for some other cancers, but one of the great hopes is that some of these new genes that we've found could be useful in preventing cancer. And it doesn't necessarily matter that they're rare, even if there are only 1% of cancers, by using those and changing those in a normal individual before they have had cancer then we may be able to reduce that risk.   So, there are lots of potential new targets for prevention that are coming through and as David said it is going to take a lot of work to work out which of those are deliverable and who will benefit. But we have quite a lot of opportunities in that space and although that may not be us that takes that forward, it may be, but it may not be. We think it is a lot of material for those interested in chemo prevention using drugs of cancer that they can work on and with luck deliver some new ways of preventing cancer that may be simply popping a pill every morning to take your risk right down to as close as zero as we can.  Helen: Thank you Ian. David, I think you had something to add here.  David: Thanks Helen. One area of prevention that we're really interested in Oxford and many others are is using the genetic alterations that we find in bowel cancers and other cancers as targets for vaccination. Now we know that gene alterations will cause abnormal proteins which while they might drive the cancer, make it grow or not die, can also be recognised by the immune system so the abnormal proteins can be recognised by the immune system as being foreign and as foreign they can be targeted by the immune system so the immune system will try and kill the cells carrying those alterations. And we know for some sub-sets of bowel cancers those alterations can be relatively predictable actually, they occur in quite a sizeable fraction of some sub-groups of bowel cancers.   And one area that we're particularly interested in at the moment and actively pursuing is using those targets where you need some additional work to demonstrate when they are particularly recognisable by the immune system. But to use these genetic alterations is potential targets for vaccination with the intention ultimately of preventing bowel cancer in at risk individuals or ideally in the full-term time the whole population. And we've received some funding from Cancer Research UK to pursue this line of research and we have a group working on this in Oxford and as I say many others do elsewhere.  Helen: Thank you David, yes I have a vested interest in this because my understanding is this work is aimed primarily at people with a genetic condition called lynch syndrome which predisposes the people who have inherited this gene change alteration to bowel cancer, womb cancer and other cancer. And I had womb cancer, as I think David you know, a few years back and discovered it was due to lynch syndrome and so it's really exciting that you're now looking at vaccinating preventing because yes I take aspirin every day, I have my colonoscopy every 2 years which have some effect on preventing these cancers but it's not 100% guaranteed. And I don't suppose it ever will be but having the vaccination in that armoury would be fantastic I think for future generations, it's very exciting and we look forward to hearing more about it.   Thank you Ian and David. I mean we've heard a lot there about preventing bowel cancer but I think moving back now to potential treatments, you know, we've heard from David how this study has shown a number of actionable findings but what are the next steps towards treatment? How can these findings be turned into real actions that will benefit those people diagnosed with bowel cancer in the future? Ian, perhaps you would like to pick up on this to start.  Ian: That step is one, you know, in which I'm not personally an expert but a lot of the newer treatments are based on the finding of so called driving mutations which are simply genetic changes that occur as the cancer grows and contribute to that growth and ultimately if it's not treated to the spread and dissemination of a cancer. And the fact that we have reported 250 which need validation but of which a large proportion are likely to be true drivers means that anyone of those can be a potential new target.   The criteria to be used for which of those mutations to pursue, which of those driver genes to chase up are quite complicated normally, depend on many things such as the interest of research groups and small and larger drug companies. And the similarity of those genes to other genes that have evolved and the processes that they make to go slightly wrong in the cancer.   So, there is also the issue that because these are uncommon, everybody talks a lot about personalised medicine or precision medicine, this would be truly precision or personalised medicine because a genetic change that was driving the cancer in only 1% of patients is obviously not a huge number of patients although bowel cancer is a common cancer so it's not a tiny number either. But it would mean investment at that level to benefit let's say 1 to 2% potentially of all patients with bowel cancer but I think that's a nettle we have to grasp. And I think our results are showing that most of the really common drug changes either have not yet been successfully targeted in treatment or are too difficult to target.   So, we're going to have to start looking at these less common genetic drivers and design strategies, inhibitors, you know, again that can be delivered to patients relatively straightforwardly in order to see whether they benefit the patients concerned. But there is this problem of getting enough patients enrolled in clinical trials where a change is only present in a relatively small proportion of all the patients with that cancer type.   Helen: Thank you Ian. Presumably if there is a relatively small number of patients the people who are looking at running these trials might be looking at perhaps international trials, would that be one way to go?  Ian: So, I think David can speak with more personal knowledge but there are international trial networks and there are collaborations along these lines already under way. I would hope that those could be made use of even more than they are already. There is, you know, a financial consideration for those developing new anticancer treatments which are, you know, high risk work and also the costs of setting up trials and enrolling people is not a trivial thing. So, I think those are hurdles that can be overcome but it would need a concerted effort to do that. Patients will play a major role in that and patient organisations as well as 100,00 Genomes and other similar projects.  Helen: Yes, thank you, David I don't know if you want to come in on that.  David: Yes, the challenge of testing therapies in small groups is a very real one and there is lots of interest at the moment in exploring alternatives to conventional clinical trials. And as we use more electronic patient records and we have pharmacy records so there is the potential to get those data from routine clinical practice and there is lots of investments and attention on that at the moment so called real world data which is always an interesting term as if patients in clinical trials aren't in the real world which of course they are.   But it's perhaps a little more cost effective sometimes in clinical trials, of course it does pose its own challenges in how you disentangle true treatment effect from other factors because there are many factors impacting on how long people with cancer live. But there is a lot of investment and effort going into that at the moment and it will be interesting to see how that develops over the coming years.  Helen: Turning to you Claire based on your experience how well do you think people with bowel cancer understand how genomes can help with their care and what support is currently available to them in this area?  Claire: I think the answer, as it is so often is, it's dependent on individuals and not just one individual. So, I think some patients are very motivated to know as much about this as possible and to understand and to know what the next steps may be in their own treatment that may be helped by this. Others don't want to have the same knowledge and want to be guided very much by their medical teams but I think oncologists obviously are at the forefront of this and we see at the charity … we have services at the charity that supports patients and we see lots of queries into our ask the nurse service where people have been given variable information about I suppose personalised medicine as Ian alluded to and how their very specific bowel cancer may be treated, so I think it varies from patient to patient.   There is support available so we have the ask the nurse service I alluded to. We have a brilliant patient forum actually and everybody in clinical practice will have seen this, patients often become more expert than anybody and they share advice and they're moderated forums that are a very safe place for people to ask questions where there is a moderator to ensure that it is made really clear that circumstances are individual.   And the same with the ask the nurse service because you don't have all the clinical information so it is about empowering people, so there is support available. I think the other thing that is really important is equipping specialist nurses with the knowledge that they need to support their patients. This is a really exciting area of evolution for bowel cancer particularly I think in all cancers at the moment but for bowel cancer I think things have changed fairly rapidly in recent years and specialist nurses really need support in knowing that they have up-to-date information to give their patients.   So, that's another challenge for us and any specialist nurses that might be listening to this podcast we have online education on genomics for specialist nurses. Just while we're talking about that and you mentioned lynch syndrome earlier, so there has been a lynch syndrome project as I'm sure you're aware where we're trying to get testing for lynch syndrome brought into local hospitals.   So, there was some funding via NHS England so that the testing be done at time of diagnosis, so a pre-test and then a final test if that's appropriate, for everybody diagnosed with bowel cancer to see if they have lynch syndrome. And in some trusts that has been done and in others it hasn't yet and the funding hasn't quite followed in the way that we need it to enable that to happen. It's vitally important, we think there are about 175,000 people in the UK with lynch syndrome and we only know about 5% of them. And this is a gene change that is an inherited gene change so we can do what we call cascade testing where we test family members and we can then employ preventative strategies to prevent people from developing bowel cancer.   So, it's a really important project, so I think as well as supporting patients with the information around the changes that are happening in this area we also need to ensure that we support the workforce and have investment there to enable the support of all the changes and the genomic landscape.  Helen: Absolutely Claire and so much resonates there with what you've said. Having myself had cancer discovered that was due to lynch syndrome, cascade testing offered to my family members so valuable. It turns out I inherited my change from my mum who is 83, has never had cancer, so I think that's a very good example of, you know, it doesn't necessarily mean that you will get cancer but actually on that point that you made about empowering patients I always have a right smile because there is my mum going off to all her other medical appointments because at 83 she sees quite a few people and she is always the one telling them about lynch syndrome and educating them because most of them haven't heard of it, so yes it's really, really important.   And that patient forum, you're probably aware of Lynch Syndrome UK, I don't have any involvement in that other than being a member but that is so valuable for people with a particular condition to go somewhere where they can talk to or listen to other people with a similar condition, really, really valuable.   Right, well I think circling back really to the 100,000 Genomes Project I think you touched on this earlier David but reflecting on what you and Ian have told us about your study what is it about the 100,000 Genomes Project bowel cancer dataset that made this work possible?  David: There are a few things, one of which and not least of which is the sheer size of the effort. So, to have whole genome sequencing for more than 2,000 individuals is previously unprecedented and we'll be seeing more of this now as we scale up our research efforts but at the inception of the project it was very, very ambitious and to be able to deliver that is a huge achievement. And the quality and breadth of the analysis is very strong as well.   And ultimately, you know, the former gives thanks to the people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldn't benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what we're seeking to realise now. But, you know, it's not a given when we treat people in the clinic so we're very, very grateful to those individuals.   And I think also to the scientists who worked incredibly hard over the last 5 years to deliver this work actually. So, having been part of the team and being lucky enough to be part of the team along with Ian we've had hugely motivated individuals that really have dedicated a large fraction of their working lives to delivering this project which I think is a fantastic achievement as well.  Helen: Thank you, thank you to all those participants who at a time when their lives probably were turned completely upside down by a cancer diagnosis were offered the chance to join the 100,000 Genomes Project and said yes. As you say most of them will have known that it won't have helped them but by donating their data, you know, it has allowed this work to happen and potentially it could change lots of people's lives in the future, so thank you to them.  Ian: Could I also just emphasise and agree with what David has said, I won't go through all the individuals by name, but if anybody wants to read the published report of the work there are several people on there, Alex Cornish is the first author, but many colleagues from an institute of Cancer Research, The University of Manchester, Birmingham, Leeds, other universities in London that all contributed, but also colleagues in the NHS and/or universities who recruited patients, collected samples, processed them etc and of course the people who did the preparation of the samples in genetics laboratories and actually did the sequencing and basic analysis too.   So, it is a truly huge effort across particularly all the cancer types which is particularly a complex collection given the fact the tumour is needed and a blood sample. It's quite difficult in a way to find a formal way of thanking them for all of this but without them it wouldn't have happened.  Helen: On that note I think we'll wrap up there. A huge thank you to our guests, Professor Ian Tomlinson, Clare Coughlan and Dr David Church for an enlightening discussion on the groundbreaking study published in nature. This research is set to reshape our understanding of colorectal cancer and pave the way for new possibilities in treatment and patient care.   If you would like to hear more like this please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand. 

On this episode we are joined by Alex Mackenzie, an occupational therapist and certified hand therapist. We discuss flexor tendon rehabilitation, how things have changed over the years to optimize outcomes for our patients, how to progress patients through their rehabilitation, and important factors to consider when treating these injuries. Guest Bio: Alexandra MacKenzie OTR/L, CHT is the Clinical Lead at Hospital For Special Surgery and she serves on the board of the American Hand Therapy Foundation. Her clinical passions are brachial plexus/ nerve injuries, flexor tendon rehabilitation, and mentorship. She helped develop an AOTA-accredited hand therapy fellowship program at HSS and enjoys being the clinical mentor for that program. She has written chapters and presented nationally on a variety of hand therapy related topics. Global health and global healthcare education are interests of hers and she has participated in short-term medical missions to Guatemala, Honduras and Fiji.

In this week's episode, Han is joined by David Coyle. David is a Consultant Psychiatrist, and the Clinical Lead for Adult Eating Disorder Services across multiple Trusts in Northern Ireland. With a career spanning 18 years in mental health and 7 years specialising in eating disorders, David is dedicated to his clinical work, especially where he can be creative and innovative. He is also passionate about teaching and provides training for various healthcare disciplines in the region. One of his notable interests is the introduction of Mentalisation Based Treatment (MBT) as part of the treatment options available within his service, which focuses on severe and complex eating disorders.The concept behind MBT and why this is useful for individuals with eating disorders.How does MBT differ from other types of therapy models e.g. CBT, SSCM-ED, MANTRA.What takes place in an MBT group session in David's service and the outcomes they have witnessed.The importance of engaging loved ones in therapy to ensure holistic support and wrap-around care.The impact of MBT on understanding one's own emotions and the impact that our emotions can have on others.The importance of understanding emotions and the diversity each emotion has and can take shape.How to navigate your recovery and therapy if others in your network don't want to engage in therapy or express emotions.How services can introduce MBT into their practice.Please note that this podcast explores topics some individuals may find difficult to hear and should not be used as a replacement for professional advice. If you need further support after this podcast, please consider talking to someone you trust. You may also wish to reach out to your GP or mental health professional.We've included a list of additional support options in case you need them:Samaritans are here for whatever you are going through. You can call free any time, from any phone, on 116 123.FirstSteps Eating Disorders is an eating disorders charity for children and their families, young people, and adults affected by eating difficulties and disorders. You can call them on or email info@firststepsed.co.uk.Beat Eating Disorders is an eating disorder charity offering support for those with or supporting someone with an eating disorder. You can call their helpline for free on 0808 801 0677 (England), 0808 801 0432 (Scotland), 0808 801 0433 (Wales), 0808 801 0434 (Northern Ireland).

Jason is a key player at LJC, leading our Signature Skinny Shot program and overseeing patient care efforts in the pre-op area and recovery room. Jason's nursing background and expertise in health education make him the perfect guide to help you achieve your weight loss goals, offering tailored advice on eating right, exercising, and feeling your best. He's with you every step of the way, ensuring you're on track and satisfied with your results.Read more about Jason Whaley, AAS, BS, RN, NRPLearn more about the Signature Skinny ShotLearn from the talented plastic surgeons inside La Jolla Cosmetic, the 20x winner of the Best of San Diego and global winner of the 2020 MyFaceMyBody Best Cosmetic/Plastic Surgery Practice.Join hostess Monique Ramsey as she takes you inside La Jolla Cosmetic Surgery Centre, where dreams become real. Featuring the unique expertise of San Diego's most loved plastic surgeons, this podcast covers the latest trends in aesthetic surgery, including breast augmentation, breast implant removal, tummy tuck, mommy makeover, labiaplasty, facelifts and rhinoplasty.La Jolla Cosmetic is located just off the I-5 San Diego Freeway at 9850 Genesee Ave, Suite 130 in the Ximed building on the Scripps Memorial Hospital campus.To learn more, go to LJCSC.com or follow the team on Instagram @LJCSCWatch the LJCSC Dream Team on YouTube @LaJollaCosmeticThe La Jolla Cosmetic Podcast is a production of The Axis: theaxis.io 

The Green Party's deputy leader, Róisín Garvey, is calling out what she describes as "insane" habits around children's transportation, such as kids being driven to school from just across the street. According to Garvey, this car dependency is contributing to a rising number of overweight children, with a quarter of those under nine now overweight.Joining Kieran to discuss this is Grace O'Malley, Clinical Lead, CHI Child & Adolescent Obesity Service.

Whether it be a crick in your neck, or serious rehabilitation post-surgery, the world of physiotherapy provides an excellent service that is sure to get you back into shape.Joining Bobby to discuss how to the Physio industry in Ireland is getting on and how they get started and grew their careers were Physios • David Dalton x Consultant Chartered Physiotherapist and CEO PhysioCare Ltd in Dublin· Alison Quinn- Chartered Physiotherapist and owner of the rehab rooms in Deansgrange· Dr Grace O'Malley - Senior Lecturer at the School of Physio – RSCI University of Medicine and Health Sciences, Clinical Lead of the CHI Complex Obesity Service

Questions, suggestions, or feedback? Send us a message!In this episode we speak to Dr. Roslind Watts. Dr Watts is a clinical psychologist, and a nature lover. Her work as the Clinical Lead for Imperial College London's psilocybin trial has made her one of the most prominent voices and minds in the field of psychedelic research.Dr Watts has been named as one of the 50 Most Influential People in Psychedelics. She builds tools and structures to foster connectedness after psychedelic experiences, finding inspiration for their design from nature. She co-founded the UK's first psychedelic integration group, and in 2022 launched ACER a global online integration community.We will talk about:The difference between Macro and microdosingCategorising synthetic and natural compoundsThe Importance of post trip integrationHow psychedelics are changing approaches to therapyThe condundrum of corporate interests and democratisation useRegulationACERAppropriation of indegenous practices“Doing the work” and being a tenant of your own traumaThe Default Mode NetworkMore about Dr. Rosalind Watt's ACER framework here.Now let's go on a trip!Web: www.whereshallwemeet.xyzTwitter: @whrshallwemeetInstagram: @whrshallwemeet

Dr. Lucy Johnstone is a Consultant Clinical Psychologist and worked in Adult Mental Health for many years. She has written and lectured widely on critical perspectives in mental health theory and practice. She is a lead author of the 'Power Threat Meaning Framework' (2018). Dr. Jo Ramsden is a Consultant Clinical Psychologist and Clinical Lead for Yorkshire Humberside Personality Disorder Partnership. Jo was a contributor to the Power Threat Meaning Framework, and has led the way in supporting its application to forensic settings. Key references: The PTMF website, with the main PTMF documents, along with interviews, slides, resources, good practice examples etc: https://www.bps.org.uk/member-networks/division-clinical-psychology/power-threat-meaning-framework Accessible overview of the PTMF as a basis for constructing narratives: https://www.pccs-books.co.uk/products/a-straight-talking-introduction-to-the-power-threat-meaning-framework-an-alternative-to-psychiatric-diagnosis Trauma and Recovery by Judith Herman https://www.amazon.co.uk/Trauma-Recovery-Aftermath-Violence-Political/dp/0465061710 The PTMF in forensic services: Blog by Jo Ramsden: https://pegortwo.wordpress.com/ Interview with Jo Ramsden: https://www.youtube.com/watch?v=yqUMKNdK0-o Willmott and Evershed (2018) 'Interviewing people given a diagnosis of personality disorder in forensic settings' International J of Forensic MH Reis, Dinelli and Elias (2019) ‘Surviving prison: Using the PTMF to explore the impact of long-term imprisonment.' Clinical Psychology Forum, 313 Willmott and Jones (2022) Trauma-informed forensic practice. Routledge (see especially chapter 2) Chapter 12 by Jo Ramsden and Kerry Buckley: 'The PTMF: Implications for practice within the criminal justice system' in 'Challenging Bias in Forensic Psychological Assessment and testing. Glenda Liell, Martin Fisher and Lawrence Jones(eds) https://www.amazon.co.uk/Challenging-Forensic-Psychological-Assessment-Testing/dp/1032138289

In today's episode, taken from live recordings at PREMIER 2024, we dive into an increasingly common treatment for type 1 diabetes: hybrid closed loop insulin pumps. We'll begin with a brief overview of traditional insulin pumps and explain how hybrid closed loops are different. The core of our discussion will be centered around three case studies, illustrating potential scenarios you might encounter in a pediatric emergency department and how to manage them effectively. With NICE's recent technology appraisal advocating for universal access to hybrid closed loop systems for all type 1 diabetes patients, it's crucial to understand these devices. Over the next few years, you'll likely encounter these systems frequently. We'll cover the essentials of how these pumps work, their benefits, and potential issues that might arise, such as connectivity problems, cannula issues, and handling intercurrent illnesses. Join us as we explore the revolutionary impact of hybrid closed-loop systems, which offer better glucose control and significantly improve the quality of life for those with type 1 diabetes. Dr Nicola Trevelyan has been the Clinical Lead for the Paediatric Diabetes Service in Southampton for the last 20 years. During this time, she has seen huge changes in the management of CYP with diabetes.  She has been involved in several large multicentre trials for paediatric diabetes,  helping to better our understanding of how best to use new technologies in diabetes management in children and move forward access to new treatment technologies.  She was one of the founding committee members for the Assoc of Children's Diabetes Clinicians (ACDC) in 2006 and has been on working parties for BSPED helping evidence base and re-write the national DKA guidelines in 2020 and for the National Paediatric Diabetes Audit.  For the last 4 years, she has been on the Clinical Advisory Group for the RCPCH Quality Improvement Programme for Paediatric Diabetes. 

For this week's Kids Health Check, Kieran Cuddihy is joined by Grace O'Malley, Clinical Lead for CHI Child and Adolescent Complex Obesity Service and Senior Lecturer in RCSI School of Physiotherapy to discuss the growing problem of teen and childhood obesity.

This week, Han is joined by David Coyle. David is a Consultant Psychiatrist, and the Clinical Lead for Adult Eating Disorder Services across multiple Trusts in Northern Ireland. With a career spanning 18 years in mental health and 7 years specialising in eating disorders, David is dedicated to his clinical work, especially where he can be creative and innovative. He is also passionate about teaching and provides training for various regional healthcare disciplines. One of his notable interests is exploring the treatment options available for severe and complex eating disorders.This week, Han and David discuss:David's journey as a consultant psychiatrist and how he began working in eating disorders.David's perspective on using diagnostic labels and the importance of accessing treatment.The importance of getting to know a patient and their difficulties to provide adequate recovery treatment.The need for weight restoration in recovery as well as the uncertainty this can bring in recovery.David's perspective on the descriptor "Severe and Enduring Eating Disorder" and when this may be supportive for patients.David's perspective on the Mental Health Act and when it may be appropriate to detain a patient or not.David's experience of supporting a patient with palliative care and the reasons for when this may be necessary.How to determine if a patient has the capacity to decide on palliative care. Kindly note, that this episode delves into sensitive eating disorder topics such as the Mental Health Act and palliative care. Remember to take care of yourself while listening, and always seek professional help if needed. This podcast is your bridge to insightful discussions, not a substitute for clinical guidance.

Martina Healy, Clinical Lead of the Irish Paediatric Critical Care Audit, discusses the publication of the National Office of Clinical Audit's latest report into the sector.

When you think about rural healthcare, you may not think about Scotland, but Scotland has some very rural areas that deal with similar issues we deal with in rural America.  Hear about what they are doing in rural Scotland to deliver health and wellbeing to their residents, by listening to our conversation with Dr. Emma Watson, 2021-22 U.K. Harkness Fellow in Health Care Policy and Practice Deputy Medical Director at NHS Highland. “NHS Highland delivers integrated health and social care, so it is not just about illness.” ~Dr. Emma Watson Dr. Emma Watson MSc, FRCPath, FRCPEd is a 2020-21 UK Harkness Fellow in Healthcare Policy and Practice.  A Consultant Medical Microbiologist by background and a senior clinical systems leader in Scotland, she is an expert in quality improvement and in medical education and workforce planning.  Emma is Deputy Medical Director in NHS Highland which is, geographically, one of the largest and most sparsely populated combined health and social care systems in the UK.  She is also a senior medical adviser in the Scottish Government.  In both roles her focus is on developing innovative approaches to ensuring equitable access to high quality health care services with a sustainable healthcare workforce, particularly in remote and rural areas.   Emma has led a number of major change programs including the development of Scotland's first graduate entry medical school.  Emma previously held a post in the Scottish Government as Clinical Lead for the Scottish Patient Safety Program during which time she ensured quality improvement methodology translated from the development of health policy and strategy through to implementation across the entirety of the Scottish healthcare system.  Scotland was the first country in the world to implement a patient safety program on a whole system basis at national level.  As Director of Medical Education in NHS Highland she focused on the delivery of high quality medical education as a tool to increase recruitment and attract young doctors to the region as well as ensuring there is now an established programme to encourage young people from the area to go to medical school.  During the COVID-19 pandemic she led the clinical response in her region and ensured there was a whole system approach to manage the impact of the virus.  

Iyar is the month when we celebrate the birth of modern-day Israel. And yet, we recognize the need to hold space for those who have experienced personal loss. Guest host, Dr. Naomi Marmon Grumet, The Eden Center's Executive Director and psychologist Dr. Romy Shulman, who previously served as the Clinical Lead of Chana UK, break the silence around miscarraige, exploring the emotional, practical and mikveh-related aspects of this loss and how to give/get support when the need arises.You can order a free copy of Birkat Emunah or have one sent to a friend experiencing pregnancy loss or infertility at this link: https://theedencenter.com/emuna2021/ Sign up here to receive this podcast to your inbox. If you are enjoying this podcast, please consider sponsoring an episode for $36/₪136 here.

Dr Orlaith O'Reilly, Clinical Lead for the Chronic Disease Management Programme discusses the latest HSE's Enhanced Community Care Programme annual figures which show a 16% reduction in chronic disease hospital admissions between 2019 and 2023.

Improvements in quality of life and reduced healthcare costs are just some of the benefits uncovered in a Monash University study of Australia's only residential treatment program for people struggling with eating disorders. Wandi Nerida, based on Queensland's Sunshine Coast, provides a unique model of holistic, person-centred, inpatient care. As the rate of eating disorders continues to rise, so does the need for improved treatment approaches. “We're trying to step away from that more clinical hospital feel, where everything's super sterile,” says Dr Carly Roukos, Want Nerida's Clinical Lead. “As much as possible, we try to have it feel less like a hospital and much more like a home.” In this episode of Let's Talk, Dr. Roukos shares how the pioneering model of care at Wandi Nerida was first developed, and what life's like for participants who receive treatment there. Dr Roukos has been with the centre from its inception in 2020 and has played an important role in developing the successful clinical program. “The transition from treatment to home can be really difficult,” she says. “So, we provide opportunities to practice real-life things in real-life settings to help with that transition.” This piece is key post discharge from hospital: How do we maintain our health and recovery in regular life? Dr Roukos addresses this issue and more. Find out more about Wandi Nerida Enquire about placement at Wandi Nerida Meet the team at Wandi NeridaSee omnystudio.com/listener for privacy information.

Joined by Prof Aiden McCormick, Clinical Lead for the HSE National Hepatitis C Treatment Programme

Emma Ryan who lives in Waterford outlines how she suffered a stroke in February of last year and Professor Rónán Collins, Clinical Lead for the HSE National Stroke Programme, outlines why he believes the National Stroke Strategy is not being properly implemented.

Editor-in-Chief Sue Yom hosts a British-American conversation about brachytherapy. Guests include Dr. Mahbuba Choudhury, Clinical Oncology Registrar and Stereotactic Radiotherapy Fellow at Imperial College London NHS Trust, and Dr. Imtiaz Ahmed, Consultant Clinical Oncologist and Clinical Lead at Southend University Hospital in the UK, first and supervising authors on this month’s paper, Timing of High-Dose Rate Brachytherapy with External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate Cancer Patients and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial, as well as Dr. Akila Viswanathan, Professor and Chair of the Department of Radiation Oncology at Johns Hopkins University, supervising author of two papers publishing together this month, Updated Trends in the Utilization of Brachytherapy in Cervical Cancer in the U.S.: A Surveillance, Epidemiology, and End-Results Study and Updated Trends in Brachytherapy Utilization and Disparities in the United States from 2004 to 2020.

March is Sleep Awareness Month, and with busy schedules and endless to-do lists, quality sleep often gets pushed aside. But this year, Fitbit is here to help you prioritize your slumber and unlock the power of a good night's rest. Learn more from Dr. Conor Heneghan, PhD, Senior Staff Research Scientist, and Dr. Logan Schneider, M.D., Clinical Lead for Sleep Health. Hosted on Acast. See acast.com/privacy for more information.

In this explainer episode, we've asked Helen Brittain, Clinical Lead for Rare Disease Diagnostics at Genomics England, to explain what a variant of uncertain significance is, in less than 10 minutes. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you've got any questions, or have any other topics you'd like us to explain, feel free to contact us on info@genomicsengland.co.uk.   You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/What-is-a-variant-of-uncertain-significance.docx  Naimah: What is a variant of uncertain significance? Today I'm joined by Helen Brittain, who's the clinical lead for rare disease diagnostics at Genomics England, to find out more. So first of all, Helen, before we dive into the topic, I'd like to go one step further back and ask you to explain what is a gene?  Helen: A gene is effectively a section of our DNA, which is our genetic code, and it contains an instruction, something important about how we grow, how we develop, how we function as a human. Humans in total have around 20,000 genes, which is our complete set of instructions, to tell us everything we need to know about ourselves.  Naimah: So, what are gene variants then, and do they all have an effect?  Helen: Variants are effectively differences within genes. So genes, like I said, are instructions, and they have a particular way that they're spelled out and structured, so that the body can understand them and make sense of that instruction. A variant is where there's something different about the way that that gene is spelled out or structured that could affect how it works, and basically a variant is a difference to what we expect to see.  Naimah: And do all of these have an effect?  Helen: So no, not all of them will have an effect. Some differences or variants within a gene may not affect the way it works at all, whereas others might alter that gene so significantly that it can't do its job anymore, and could be very significant for that person's health.  Naimah: And how do we find these gene variants?  Helen: Gene variants are exactly what we're looking for when we're trying to find a diagnosis for somebody. So, somebody with a rare condition is likely to have an underlying difference within their genes that would be the explanation for it. We're finding these through doing genetic testing or genomic testing, so looking at an individual gene, a series of genes, or even across someone's entire genetic code, through whole genome sequencing, and we find these variants through doing that testing.  Naimah: And this might be a good opportunity to mention our other Genomics 101 episode on genetic testing, if you'd like to find out some more information on that as well. So, moving on with the next question, how is a variant's significance determined?  Helen: Variants, as we say, come from the genetic tests we undertake, and there are a team of people who look at and try to determine what effect that variant might have on that person. This is the majority of the time the work done within the laboratory teams, through the clinical scientists, who have expertise in understanding the impact of variants within a gene, and they work together with other clinical representatives, like the clinician looking after the patient, to understand that patient's disease in as much detail as they can, to try to pull all of the information together and determine whether that variant is making a difference or not.   They would look at a lot of different pieces of information to try to work out, could this be the reason behind that person's genetic disorder? And that might be things like have we seen it before, can we predict the effect of that variant on the gene? And we have to understand how variants within that gene cause a condition to be able to match up against the variant that's seen, as to whether that would make sense for that individual. So, it's a lengthy process but an important one, to make sure that we've got the most accurate information about that variant, and the understanding about that in that person's health and development.  Naimah: So then, what would be a variant of uncertain significance?  Helen: So, the output of that clinical scientist's work looking at whether a variant is significant or not comes out into five categories, but three main groupings. What we're looking for obviously through doing genetic testing is to try to find a diagnosis for somebody, and a diagnosis would be a place where we are confident that that variant impacts on that gene and leads to the condition that that person is presenting with. So, that would be a diagnosis on one end of the spectrum of what we might find.   On the very other end of the spectrum are variants that don't make an effect on the gene, that would be benign. We would call those harmless variants, things that don't change the gene and wouldn't be expected to be associated with a condition.   And then, in life there's always a grey area, and the part in the middle, between being confident about a diagnosis on one end or being confident that that variant really doesn't impact the gene and is harmless. We have variants that we find that we do not yet understand, and that's basically because our knowledge as of when the variant is looked at is good, but it's not perfect. There could be more to learn about particular variants or particular conditions, but at the moment we just don't have enough information to be sure one way or the other. And that's really important, we've got to get it right, so we do have this grey area in the middle, which are the variants, differences in the gene, where the significance of them on that person is uncertain.  Naimah: How often do we find these variants of uncertain significance when we're trying to genetically diagnose patients?   Helen: They are relatively common for us to encounter, and that's for a number of reasons, I would say. I think that we know a lot about our genes, and our knowledge has come on leaps and bounds, and it's still improving at a rapid rate, but we don't know everything yet, so there will be areas where we haven't met a particular variant before, or we can't predict how it might affect that gene, or there's some uncertainty about it because we don't have full knowledge yet. So, it does happen relatively commonly, and it probably happens more commonly the more genes or the more information we're looking at. So a test looking across someone's genome, like whole genome sequencing, we're more likely to come across these things than if we're doing a very targeted test looking at one specific gene that we understand very well, for example.  Naimah: And how can knowing the significance of a gene variant be impactful for clinicians and the patient?  Helen: This is really important, knowing the significance of a variant is key. It's fundamental to genetic testing, because we are trying to make a confident diagnosis for somebody, and we have to get that right, because if we make a diagnosis in somebody there are lots of knock-on implications of how that information is used to inform the healthcare of the individual who has the condition, or maybe even to inform their family members, who could be at risk of the same condition. Obviously, we share our genetic information amongst our families, and so a genetic test might be used for a family member as a result of a diagnosis in one individual within their family.   And of course, in some situations, that might lead them into either needing screening for a particular condition that could happen, or being removed from screening if they don't have the genetic cause within their family. Equally, people might make choices surrounding whether to extend a family or reproductive choices around the knowledge of a genetic condition within a family. So you can see, the implications are huge. It's really important this is correct.   Naimah: And finally, I just wanted to ask, can we reclassify variants of uncertain significance?  Helen: Yes, there's real need to do this because people are wanting genetic diagnosis answers for understanding, and for all of the implications we just mentioned about why are diagnoses important. So yes, we can reclassify variants of uncertain significance, and that can happen in different ways. It's not always possible straight away, unfortunately. So, what we often need is time, and that is time to understand that variant a bit better, and that might be through seeing it again in other people, maybe who have the same pattern of health problems or same picture in terms of their rare disease, and we start to understand, okay, that might actually add up to suggest that that variant is affecting the way that gene is working. Or equally, we might see it in other people who don't have the same rare disorder, so we're starting to see, well actually, maybe it's harmless and it's just part of the natural genetic differences we all have.  The other way that we can understand variants of uncertain significance better would be through research, so for example researchers looking at designing studies to try to see if they can make a model, for example, with an animal who might have the same type of variant, and see if that causes an effect on their health, so learning specifically about that variant through research could also help. And there are things that clinicians also actively try to do, and this is why we work together with the clinical scientists is to understand, are there other people within the family with the same rare condition, and would it help to test them to see if they also share the same rare variant. And sometimes that can help, not always. So yes, we really want to try to reclassify variants of uncertain significance, and as far as possible, we will, but sometimes they do just need that time for us to build that bigger picture.  Naimah: That was Helen Brittain explaining variants of uncertain significant. I've been your host, Naimah Callachand, and if you'd like to hear more explainer podcasts like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

ONCE UPON A GENE - EPISODE 219 Genomics England Clinical Lead for Genetic Counseling - Amanda Pichini Amanda Pichini is a genetic counselor from Genomics England, here to share their initiatives and mission.  EPISODE HIGHLIGHTS What is your role at Genomics England and how did your career develop? I work at Genomics England as the Director of Clinical Implementation and I'm responsible for the strategic clinical leadership for our products and services, ensuring research, diagnostics and clinical programs we support are in line with the latest healthcare standards and research. Prior to joining Genomics England, I worked as a genetic counselor, a profession I was interested in for a long time. When I started studying biology, I was keen to do something that allowed me to communicate and speak to people, but still be immersed in science. While my role isn't patient-facing now, I bring my genetic counselor skills to understand the complexities of genetics in healthcare and how we communicate to various audiences to design and deliver our programs. What are the current initiatives at Genomics England? Since the 100,000 Genomes Project, we are focused on working with the NHS to provide genome sequencing as a standard clinical test. We've worked hard to ensure healthcare professionals understand how to help families through the process, manage their expectations and potential results of genome sequencing. We're also focused on looking at different types of sequencing technology we can use to enhance the testing and care for cancer patients, and also a newborn genomes program which is part of a large-scale national research study called the Generation Study. This study will sequence the genomes of 100,000 newborn babies with a goal of understanding if sequencing in the newborn period can help identify rare conditions earlier in life, with the ideal goal of improving the quality of life and outcomes for the babies identified as having a rare condition. Can you talk more about the newborn screening? Like in the US, we do a heel prick when a baby is about 5 days old at the parent's discretion. We recommend it as public health and to look for rare conditions that could be treated if found early. We currently test for 9 conditions, but the Generation Study is an optional screening in addition to standard newborn screening. It will be available to parents at different hospital sites, a baby doesn't already need to be ill and parents don't have to have a known history to participate. At birth, a small amount of cord blood will be taken and that sample used to carry out genome sequencing and to look for around 200 rare conditions that we feel would have an early intervention option if found through screening. We will follow up on every test, with much closer monitoring and follow-up where a condition may be positive. LINKS AND RESOURCES MENTIONED Genomics England https://www.genomicsengland.co.uk/ Genetic Alliance UK https://geneticalliance.org.uk/ Genetic Alliance US https://geneticalliance.org/ CONNECT WITH EFFIE PARKS Website https://effieparks.com/ Twitter https://twitter.com/OnceUponAGene Instagram https://www.instagram.com/onceuponagene.podcast/?hl=en Built Ford Tough Facebook Group https://www.facebook.com/groups/1877643259173346/

29 February marks Rare Disease Day. This day is an opportunity for the rare community to come together to raise awareness of the common issues affecting those living with rare conditions. A rare condition is a condition that affects less than one in 2,000 in the population, and although rare conditions are individually rare they are collectively common. It is estimated that there are over 7,000 rare conditions. Around 80% of rare conditions have an identified genetic origin. In this episode of the G Word, our host Julia Vitarello, Founder and CEO of Mila's Miracle Foundation, is joined by Rich Scott, Interim CEO for Genomics England, and Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England, as they discuss challenges for those living with a rare condition and the work being carried out across the genomics ecosystem to support them. Julia is the mother of Mila, a young girl who was diagnosed with a rare genetic condition called Batten Disease, and in this episode Julia takes us through Mila's story, and how she hopes to help many more families access treatments for their children.   "So when parents, children, are diagnosed whether it's a fatal or life-longing debilitating or difficult disease, if you know that what's being learned from your child both from just the genomics to the potential treatments that's helping the next child, that helps parents like me be able to continue living."   You can find out more about Mila's story in our previous podcast episode with Rich Scott, Julia Vitarello and Dr Tim Yu.   You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Rare-Disease-Day.docx  Julia: Welcome to the G Word So my life at that point seemed to just disappear in that moment, all the things that had mattered to me were gone; I knew there was something wrong with my daughter but I had absolutely no idea that a typical child who was outgoing and active and verbal and had friends could suddenly lose all of her abilities and die. My name is Julia Vitarello, and I'm your host for today's episode. Today joining me in conversation is Rich Scott, Interim CEO for Genomics England, and Ana Lisa Tavares, Clinical Lead for Rare Disease Research, also at Genomics England. Today we'll be discussing challenges for those living with a rare condition and the work being carried out across the genomics ecosystem to support them. If you enjoy today's episode, please like, share and rate the G Word on wherever you listen to your podcasts. The 29th of February marks rare disease day. This day is an opportunity for the rare community to come together to raise awareness of the common issues affecting those living with rare conditions. A rare condition is a condition that affects less than one in 2,000 in the population, and although rare conditions are individually rare they are collectively common. It is estimated that there are over 7,000 rare conditions. Around 80% of rare conditions have an identified genetic origin. Before I get into speaking with Rich and Ana Lisa, I wanted to share my story and my daughter, Mila's, story. My life as a mother started really like anyone else's, my daughter was perfectly healthy, her name is Mila. For the first three or four years of her life she was like any other kid. I live in Colorado in the United States, my daughter was a skier, she was a hiker, she was rock climbing, she was incredibly active and singing songs and swimming and riding bikes. But around four years' old she started tripping and falling, she started pulling books and toys up closely to her face; she started being covered in bruises, getting stuck on words and repeating her sentences and I brought her to about 100 different doctors and therapists around the United States to try to figure out what was going on with her. Around four years' old I started speaking with orthopaedic surgeons, with ophthalmologists, with neurologists, with speech therapists and each one of them, you know, told me pretty much that I was a crazy mom and that my daughter was typical and normal and that she would grow out of these sort of strange symptoms that she was having.      By the time that she was six years' old, I had had enough and I was crying on a regular basis, no doctor could help me and I was tired of lugging my daughter, who was now covered in bruises and tripping and falling and stuttering, together with my newborn son at the time, kind of around the country only to be told that I was crazy. And at that point at six years' old I brought her into the emergency room in the Children's Hospital Colorado, near where I live. She was in there for about a week and underwent a battery of tests and at the end of that week I was told that my daughter had a rare genetic condition called Batten Disease and that she would lose all of her abilities and die in the next few years. So my life at that point, first four years of my life seemed to just disappear in that moment, all the things that had mattered to me were gone. I knew there was something wrong with my daughter but I had absolutely no idea that a typical child who was outgoing and active and verbal and had friends could suddenly lose all of her abilities and die. After crying on my closet floor pretty much most of the day for a few weeks I picked myself up. I started to read white papers, I started to go online and learn about other rare conditions. I started to speak with parents that had fought for their children with physicians, with researchers, and did everything I could to kind of figure out if there was even a glimmer of hope. And what I was told at the time at the end of 2016 was that there is almost nothing that could be done and very little was known about my daughter's form of Batten Disease. But that there was a tiny glimmer of hope that we could maybe stop genetic disease, and that's all I needed. I started Mila's Miracle Foundation, which is a non-profit organization. I started telling Mila's story and taking care of my kids by day and trying to fight and learn and raise money by night and I started a gene replacement therapy because it was the only option that I could take on as we didn't know much at all about the disease, and by replacing it, it was kind of the only thing that I could do, but it was going to take many years and millions and millions of dollars and I knew that it wouldn't be in time for my daughter. Along the way, there was something a little bit unusual which was that my daughter had an auto recessive disease which meant that she needed to have a mutation in the same Batten causing gene from her mom, myself, and her father, and they could only find one of these two. That led me to learn about whole genome sequencing, which was kind of the most extensive way of looking at Mila's genome to figure out where this missing mutation was. And in that search I crossed paths with a Dr Timothy Yu at Boston Children's Hospital, and he volunteered with his lab to help me find this missing mutation that no other lab could possibly find. And within a few months and a lot of work, a lot of late nights and weekends and staring at screens, through whole genome sequencing, the team was able to find Mila's missing mutation and finally diagnose her fully with this rare form of an already rare Batten disease. That is where Mila's story changed and turned direction. At that point, a recently approved drug for spinal muscular atrophy was on all neurologists' minds at that moment because it had just been approved in the US by the FDA and in other countries, and it was a game changer, these children were dying and on respirators and in wheelchairs you know at the age of two and with this new drug they were actually living, many of them were living long lives and were active and happy and healthy and going to school. And Mila looking her whole genome sequence was able to kind of fit that same criteria, and so the doctors, including Dr Yu said, “What if we did the same thing for these children? What if we made a drug like this for Mila?” This drug called Antisense Oligonucleotides, or ASO seemed to be a good fit for Mila's mutation. And so a drug was made for Mila and named after her called Milasen and it was a race against time for an entire a year with a team of honestly hundreds of people across academics and industry, I was fighting to try to raise the money and awareness and working with a scientific team. And one year after Mila was diagnosed when she turned seven years' old, we moved to Boston and Mila began receiving Milasen, which was named after her, and only in that moment in time did I realise not only what a big deal this was for me as her mother, but what a big deal this was for science. She was the first person in the world to receive a medicine that was tailored just to one person and it was named after her because there was no-one else in the world they could find that shared that same mutation. When Mila began this, you know, I didn't know what to expect but I knew that she was going to lose all her abilities and die if she didn't receive this. And so once she started receiving this within just a few months, her 30 seizures a day went down to nothing; she had occasional small tiny seizures that were barely visible but her quality of life was incredibly you know improved, not to mention our family's because she was no longer thrashing and smashing her arms and legs up against walls and tables. She had been slumped and could no longer sit up. She could no longer hold her body up and take steps with my support from behind and after Milasen she started being able to do that even walk up the stairs with alternating feet with me supporting her from behind. She also had received a G-tube and was receiving all of her nutrition through the G-tube and after Milasen she started eating by mouth, it wasn't perfect, but she was eating pureed foods, and being able to swallow better and probably most importantly she was able to smile and laugh at the funny parts in the books and the stories that I had been reading and singing to her and that she had kind of really not been responding to as much before Milasen and some of that came back. So, a year into this everyone was quite shocked that Mila had done so incredibly well in this first year despite how progressed she was, progressed her condition was. Unfortunately in the second year it was during COVID and it was unclear whether or not Mila's disease had kind of stopped or whether it was slowly progressing and in the third year Mila started having problems associated with her rare condition and I was faced as a mother with the most horrible decisions anyone should ever, never, never, never have to face to decide what Mila would want if she were able to talk and tell me whether or not this was a life that she felt like she would want to live. And after three years on Milasen, which was three years ago almost this week, Mila died and in many ways my life as I knew it was kind of over. I'm a very positive happy person and I have a son and I continue getting up every day and pushing through the day but I'm not sure how any parent makes it through days, weeks, months and their whole life without their child physically there with them. Ana Lisa: We can really hear the perseverance that you had to get a diagnosis through whole genome sequencing eventually for Mila. Can you tell us a little bit more about that process and what that diagnosis, what did it mean for Mila and for your family? Julia: When Mila was first diagnosed with Batten Disease, one of the missing mutations could not be found by any lab. I did research and found out that whole genome sequencing which at the time was very, very hard to find a lab that would do it or anyone that would do it in the United States, I did learn that that was really what was needed in order to try to really get down to find the underlying genetic cause of Mila's disease and give her a full diagnosis. So once we managed to have Dr Yu's lab at Boston Children's Hospital carry out the whole genome sequence, obviously we were able to then find exactly where the broken, underlying broken kind of genetic mutation was and why that was important was for two reasons: 1) was so that we could actually have a diagnosis and even though it was the worst diagnosis we could have ever asked for, at least there was an answer and for so many years I didn't have an answer and there is nothing worse than seeing your child, you know, having all of these different symptoms and problems and having you know tens, if not hundreds, of different doctors and therapists tell you that they don't know and maybe you're just a little bit over-worked and over-worried about things, and having no answer and no idea what's wrong is like living in this limbo that's just terrible. And so whole genome sequencing allowed for us to have a full diagnosis for Mila, and it also allowed us to use that data since it was truly the precise place where, you know, we could find the precise plan where her gene was broken. It allowed the researchers to then also think about what could be done about it as well, which is the second thing a parent thinks about after they have the kind of relief in some ways, which is a strange word to use but it's true, of knowing what is wrong and then thinking, “What could I do about it now?” And so for me I would say that's how, Ana Lisa, that's how I reacted to that, is there was enormous relief initially, which is just the weirdest word ever to use for that but at least I felt like I wasn't crazy and that there was an actual reason and that it allowed us, allowed me and others to think what kind of action can we take now. Rich: One of the things that often strikes me, I'm a clinical geneticist by background, just like Ana Lisa, is how often particularly several years ago when we were in a different situation, it depended on families and parents pushing and pushing and pushing and asking, that's something I think in the UK we're really lucky that there have been changes in terms of availability of testing. Julia, as you know, we were set up ten years ago initially to run a project, a research project in partnership with the NHS called ‘The 100,000 Genome Project' asking the question about whether whole genome sequencing could be used in a diagnostic setting. Whole genome sequencing had just emerged as a thing that could even be conceived of as affordable in a healthcare system back then, and we worked with the NHS and tens of thousands of families with rare conditions and people with cancer to ask that question and again, we're really proud of what that work and our partnership with the NHS has led to, which is now in the UK. There is the availability nationally of whole genome sequencing to test in certain settings including in rare conditions that are hard to solve in this sort of way and it's one of the things which has really changed the way we can go about this, but we also know that there's still, it's still hard often to identify who should be seen by a specialist who might do a test and so on. But it has really changed things and I think it's hearing from families like yours about how challenging it is and thinking about how we turn, looking across all of the story that you told us of everything you went through, how we can make that be something where we can make it be more systematically available and work for many more people, and I know your phrase from Mila to millions really strikes a chord with me, and I know with the NHS mind-set here in the UK where it's about equity of access and I think that mind-set that you bring is so important. Julia: Yes, Rich, I think it's a really good point you know, because a lot of parents like myself, we're talking about probably millions around the world and tens of thousands just in the UK alone, spend so much time going from one physician to another and to a therapist and it takes an enormous amount of energy and time in a family that's already dealing with pain and confusion and not understanding what's going on, not to mention usually that child, in my case, Mila, is having problems that it's not easy to leave the house and get in the car and go to all these appointments. And the more we can push towards whole genome sequencing as one of the first places to go, if not the first place to go, the more it's going to cut that sort of diagnostic odyssey down to the very bare minimal. And so of course a dream would be is that any child that has, I like to think of it as soon as you kind of have more than one symptom that shouldn't normally go together, that sort of has a little red flag that goes off and in most parts of the world right now no physician wants to scare a parent like me, it's happened a number of times to me where a physician has said, “Well, you know, there is this rare condition but I'm not going to bring that up because it's so rare that the likelihood that your daughter has that, I wouldn't want to scare you.” But the more we can move towards whole genome sequencing right away to help with that answer that could cut months and very often years from that odyssey, and that is where we need to be, we can't have the tapping on the knee and stacking up blocks and running down the hall for months and years just to figure out what's going on. Ana Lisa: And I think Rich also there said a power of having a national healthcare service where patients who are having whole genome sequencing can also decide whether they wish to consent to be part of research and combining that with a national genomic research library and then the ability to work so closely with the NHS and go back to patients if there is a new diagnosis that could benefit them is really powerful I think, and that's definitely one thing that we've also learnt from these big whole genome sequencing efforts is that our knowledge is continuing to develop and some people will get a diagnosis from that immediately and we've got amazing colleagues working on diagnostic discovery looking at whole cohorts of patients now who are having whole genome sequencing and that's also been really informative and allowed a lot of new diagnoses identified also through research and through these efforts to be found. Julia: Absolutely and I think that the UK is incredibly well suited to have such widespread sort of country-wide whole genome sequencing project like what Genomics England has done because you have one system where all of the clinical and genetic data can all come in and kind of be analysed both for like you said diagnostics but also it could be, if families and patients are interested, right, in contributing to the research which then comes full circle and helps the entire system benefit from better treatments you know and better understanding of diseases. Rich: And that point of sort of thinking about how to move things forward, so the NHS has a service based in Exeter which is addressing the question where children are on intensive care, where often intervention is needed really rapidly to make a difference, so that's one of the examples where sort of thinking about making sure that service is available early and rapidly is being set up and that's been really successful and identifying a cause where that really changes the care of that child on intensive care. The other area where we're working really closely with the NHS at the moment, as you know, Julia, and in fact I think this was probably one of the reasons we first came to talk to you was thinking about our newborn genomes programme where if you like, the big question there is saying we know that there are a few hundred conditions that are within that longer list of rare conditions where there is a treatment available routinely if the diagnosis is made, and saying could we use whole genome sequencing alongside existing newborn heel prick testing which in the UK currently looks for nine, shortly to be ten, conditions. So we're just about to launch that programme and that will sequence the genomes of 100,000 babies born at maternity hospitals, not selected for children where there's something, a concern, raised, but any baby at that hospital would be eligible for the family to choose to join that research programme and really to ask that question about whether this is something that we should offer to all babies developing the scientific evidence around it, learning about how you might implement it in practice, and also having conversations about how one might do that, what public attitudes are to it and so forth, developing evidence that can move us forward in that area too. And back to Ana Lisa's point about improving knowledge, we know that today there are a certain number of conditions that one might think are comparable to those nine that are currently looked for in the UK on the heel prick that we could use genetics as a way in. We also know that through the sort of innovation and the new knowledge that you mentioned that was relevant to Mila, that list might grow quite considerably in the coming years, so it's thinking about how we set ourselves up to make sure that we're able to take advantage of that to its full. Julia: Yeah, and I think it's a great, I'm glad you brought this up Rich because the UK really is leading the world in this, there is no-one else that is doing whole genome sequencing at birth, and ultimately, that's where we need to be. You know it's not going to happen overnight and like you said, the purpose of this is really to learn a lot about how and if to roll this out maybe in a larger scale way across the UK. But ultimately, you know, as Mila's mom, I think all the time about you know how incredible what I saw at a very progressed state for Mila with this treatment and the only way to actually really truly help Mila and other Milas is to get to these children early enough so that they're diagnosed before they have symptoms and they're treated before they have symptoms. And the way to move towards that is to at least have efforts like the project, you know, the newborn screening project so that we can get to children, find them before they have symptoms, treat them before that and from what I saw from Mila I feel pretty strongly that if Mila had received Milasen at birth she might never know the effects of Batten Disease, and we as a family might never know what it's like living with a rare condition, and this is a step in that direction to help. Effie Parks: Hi there, I'm Effie Parks, mom to Ford, who lives with a rare neurodevelopmental disorder called CTNNB1 and the host of the Once Upon a Gene podcast. Our show connects families facing rare diseases, offering stories from parents, insights from experts and discussions on everything from navigating grief to exploring genetic advances. It's a space for understanding, connection and empowerment. For support and inspiration on your rare disease journey, subscribe to the Once Upon a Gene podcast on your favourite podcast app and let's navigate this path together. Ana Lisa: Julia, I'm interested to hear what you think the development of individualised medicines like the N1 treatment Mila had what that means for the sort of collaboration that's required across the genomics ecosystem to achieve that. Julia: Yeah, that's a really good question. It's been seven years that I've been thinking about this kind of individualised medicine concept, you know, as Mila kind of became the pioneer in this field and I'm not a scientist, I'm not a physician, but I've learned a lot because I've been fortunate enough to be part of thousands and thousands of conversations, including with all of you and others, Genomics England, and around the world and I think what I learned and what I've learned so far is that when you have a genetic condition most genetic conditions are individually rare and unfortunately that doesn't make them very suited to have anyone go after a treatment for them because really the only way to connect a patient, a child like Mila, to a science or technology is if they're lucky enough, and I hate to use the word ‘lucky' but they're lucky enough to be part of a large kind of cohort of people, and that allows them to be, you know, commercially viable, so a company will be maybe develop if they're lucky, a treatment for that, for those people. The only other option is this sort of like Herculean effort of which myself and Dr Yu and others went through, we had to raise millions of dollars and get hundreds of people to get on board and develop a novel medicine for one person – now how scalable is that? How many times can we do that, right? And so the only people that really have access to medicines today with genetic conditions are those that are fortunate to be part of one of these two groups, but what about everyone else which is 95% of the people? And so I think what the field is learning is that we kind of have the patients and we're finding them, especially thanks to Genomics England and others, we're starting to find them more rapidly earlier, more of them, and we have these technologies to be able to not only find them but to also treat them but we just do not have the infrastructure and the processes to connect them, we have clinical trials and we have these sort of named patient route but we don't have anything else. And so I think the genomics community, especially in the UK because it's so well suited with all the efforts that we've just brought up, is really well suited to kind of try to work together to allow for access kind of no matter how many people could benefit, it's not only one, it could be six or 20, or 200 or 500. Right now there is no access for them. So I think that the UK is really well suited, starting with whole genome sequencing, that's where it begins, it begins by identifying patients early enough and getting the data that's needed in order to diagnose them and also to help with the treatment you know, and so this is how I think the UK is really leading the world right now, including in the recent announcement of the rare therapies launch pad, which Genomics England is part of, I am part of, others are part of, Oxford Harrington Rare Disease Centre, the MHRA, others are all part of really trying to be dedicated to building the infrastructure and resources and processes that are needed to connect the patients to these technologies that exist today. Rich: I've been really inspired by the conversations and the drive that you, Julia, personally have given to those conversations. And I think what's really interesting and I think it's relevant more broadly than just in rare therapies particularly, but I think that challenge of recognising the need for the system to change to be able to respond to evidence and make the response proportionate to the expectations of various people, the patients or the families who are receiving it, the system as a whole, these sorts of therapies and rare conditions as well, are just not the shape that works well with existing paradigms, but I think it's relevant you know, in other settings as well. I'm really interested in some of the conversations that I've had with you before about balancing risk and understanding how to get that right and the fact that that really needs an open discussion in public to also understand the journey and the situation that families find themselves in. I wonder if you could tell us a bit about your perspective on getting that risk balance right? Julia: Thanks for bringing that up, Rich. I think it's really, really important because to me the way we think of risk and benefit and the risk tolerance maybe is a better way to put it is the foundation of the house that we're building. So, you know, the regulatory process and everything behind that are built on top of how we think about risk. And one of the things that I regularly think about is children that have end stage cancer, and that we as a society have accepted an enormous amount of risk for a child at end-stage cancer that has no other options that's going to die no matter what, probably very rapidly and that if they don't respond to kind of some of the main line treatments then to turn to an experimental cancer treatment which carries a very high risk is considered very acceptable by our society and that everyone, the clinicians, the families, the regulators, everyone is willing to take that risk for that child because they're going to die otherwise. And they're willing to spend money and they're willing to take the risk and often perhaps to buy that child maybe three or six months of life. So then if you look at Mila and if I tell you that instead of having a rare condition that she has an end-stage genetic disease, and I use the words from cancer, from oncology, is now suddenly the discussion changes a little bit, so Mila's going to die no matter what, no child has ever lived with her form of Batten Disease and she's going to lose all of her ability, so we know the risk of not treating Mila. The risk of treating Mila in this case was an antisense oligonucleotide, which is a modality that's been around for 30+ years, tested in animals and more frequently in numerous humans across different sort of trials. And the labs that worked on Mila's medicine felt that it was safe enough and hopefully efficacious enough. And at that point why is the hurdle so exponentially higher than what it would be for a child with end-stage cancer? The way that we are thinking about these children with end-stage genetic disease and end-stage cancer, is drastically different, so we need to first, to your point Rich, we need to start realising we've already set that precedent, we don't need to be having this discussion again. We know the risk we're willing to take for a dying child when there's no other therapeutic, no other option and they're going to die no matter what. So the risk of treating Mila, versus the risk of not treating Mila is black and white and we need to do our best and then we need to not only treat Mila but we need to learn from the treatment of Mila. We need to collect those learnings, they must be iterative learnings so that the next child that's treated with an individualised different ASO or different medicine that they don't happen in silos, but that all of this knowledge comes together so that the second and the third and the fourth and the tenth and the twentieth, the process gets better and faster and eventually cheaper so that it's accessible. Rich: Yes, and that's very much back to Ana Lisa's point on the link and for diagnostics too on continuing to learn and creating a system that recognises that that's crucial to offering the best care today but also in the future and being able to make proactive decisions more confidently if you're a policymaker, knowing that you'll continue to learn, you don't have to pretend you know everything today. Julia: It's very meaningful for parents. So when parents, children, are diagnosed whether it's a fatal or life-longing debilitating or difficult disease, if you know that what's being learned from your child both from just the genomics to the potential treatments that that's helping the next child, that helps parents like me be able to continue living. And so you know, research is this kind of generic word, I wish there were a better word for it. Really what it is, is it's learnings and it's what can be learned from my child that can help the next child? Ana Lisa: And then that learning requires a lot of collaboration, which is the super important part I think of your story. Julia: Yes, it does, it requires a lot of people starting with those diagnosing the children with whole genome sequencing all the way through just to the clinicians who are in the NHS, not to mention the researchers who are then looking at the data and bettering their understanding. Ana Lisa: I think there are also, maybe one can extend some of those parallels as well, in that I think currently we sometimes think of an individualised therapy of NF1 as being something that takes a lot of time and benefits an individual, and actually if we can really collaborate we can really set up processes that work across the ecosystem and keep learning, then I'd love to dream that actually this could help many, many different patients, with many, many different types of rare conditions because actually we've learnt how to target a little bit more at source, perhaps a particular type of genetic variant, and so a bit like cancer, we're not thinking about breast cancer, we're thinking about what sub-type, what genetic causes there are and targeting those, and if we can apply that one day more broadly across rare conditions then it might be that actually once you've learnt a certain amount, that you could scale up and treat many, many different conditions, not dependent on their frequency in the population. Julia: Yeah, that's a great dream, I share that dream. Rich, what is your, you've been in this for many years, what's your dream for the next five, ten years? Rich: I guess I have, I think there's two aspects to it. I think there's two, I think there's a lot of distance left to run for us improving on the diagnostics and I think thinking back to your conceptualisation of it Julia, of sort of thinking about how we can bring that earlier, whether that is that for example we're able to sort of more proactively flag when children have you know, more than one visit to a particular type of doctor or something that makes that happen much earlier in the process. So the tooling that we now know works whether it's whole genome sequencing or something more targeted can be used earlier in the process, or whether for example in our newborn genomes programme we get that evidence that we can look for a broader range of conditions in a screening context right at the beginning of life. And I think in five to ten years we should be in a substantially different place, we'll know whether or not we think whole genome sequencing should be there but offered for every baby at birth, and we can be much more proactive also when symptoms arise. I would also hope that on the side of therapies and intervention, we're in a substantially different position and I think, I've been amazed the last five years how my level of hope has increased. I believe we should now be in a position in five to ten years where those with a therapy that is potentially there to benefit them, should at least be able to be aware of it and there will be a clear pathway by which either that is available if it's proven, or there's a pathway that we all understand about how that can be trialled. And I think we're at the beginning of that journey and I now feel it's a responsibility of ours to work through how we can bring the right pieces into place, we can't prejudge the science, but we can set up the system that makes us be able to respond to it. Julia: Yeah, I remember Rich when you and I were speaking a number of months ago and maybe you could share the story because you talked about your hope kind of changing over time as a clinician I thought that was really powerful to me. Rich: Yeah, I remember it's probably now maybe 15 years ago being asked by a family about what my advice would be to them on the likelihood of there being a treatment for their child's particular condition being available and in fact they asked me to do it in a way that I sort of provided a formal written report to them that I spent a lot of time thinking about and agonising over and was very honestly you know saying it was highly unlikely that something would become available. If I had to write that same report today it would be very different. Julia: That's so promising to hear that. I don't know, Ana Lisa, have you had any experiences like that in the past that you feel differently now of how you would approach a family like mine? Ana Lisa: I think it's a real balance between having that hope ourselves, sharing that hope with other people and not giving false hope and it's such a balance when right now more than 95% of rare diseases don't have a treatment and I think that's such a difficult position to be in right now. And everything we've been talking about gives me massive hope for the future and a lot of what we're pouring our energy and efforts into is both the diagnostics so that we're not trying to make a puzzle with missing pieces in the dark and that's mission-critical, and then the real hope that actually this will drive therapies, which is what we really want for everybody who needs a therapy to have a therapy that's effective, whether they've got a common condition, a rare condition and that's our driving ideal. So I think I'm full of hope and optimism and I hope that it will accelerate, that's what I really hope, the momentum will build and we'll get to a certain level of knowledge, we're learning the processes, we're learning the evidence, we're learning the collaborative models that are needed to really suddenly explode our ability to treat rare conditions. Julia: Yeah, you know when Mila was, I guess when I look at newborn screening in the United States and Batten CLN7, which is Mila's kind of sub-type of her condition is not on newborn screening tests because there is no treatment for it, but the whole genome sequencing that was done for Mila was the data that we got from that was what was needed to create a treatment for her and so it's an unusual case where she was sequenced and a child and a baby, a newborn in the UK could be sequenced and not only told that they have a disease, so they have time to kind of understand the disease more but also potentially kind of prepare for a treatment that might be in the pipeline, but that data is also going to help scientists and researchers create new treatments that may not be available when that child is born but that's the data that's needed to create the treatment. Right now you guys are you're really at the forefront of solving both halves of the what I consider like a rare condition, you know, global health crisis with tens and hundreds of millions of people that have you know families like mine, like my story sounds unique, it sounds impossible but there are tens of millions of other people like me, like my story sounds unique, it sounds impossible but there is tens of millions of other people like me and so to have the UK kind of leading this effort to solve both halves of the problem, the diagnostic half, you know, what disease does a child have and find it in time and also kind of the treatments, here's where we're headed, and if we don't solve both of those problems then there is no such as access, you know to a better life, so I'm really grateful for the fact that you've set a precedent for other countries because now finally there are other countries that are looking towards you and kind of really trying to do the same thing that you're doing. Rich: Yeah, well I think we feel we're uniquely placed; the NHS in the UK and for Genomics England our partnership with the NHS, together with a number of other factors and I think the recognition from government as well as the NHS over a long period that the importance and the power of genomics and the importance of for example, making changes to regulation to get it right mean that it's something that I think we feel really privileged to be in the position to even be able to ask these big questions. Julia: yeah, I think the UK is really uniquely suited to have hung their hat on genomics so that the topics you're taking on are very central, they're not kind of on the sideline, they seem whenever I'm in the UK they say that what Genomics England is doing is at the forefront and in the middle of all the discussions with academics and companies and regulators and government. What do both of you think are the, what are the biggest kind of hurdles we have coming a few years in the newborn programme or you know, any of your other initiatives? Rich: I guess all of these are big questions and I think we need, it's back to that sort of point from Ana Lisa sort of balancing the hope and expectation, I think we're uniquely placed to develop the evidence really clearly and one of the things that we again think is so important is having this conversation in the public about it and developing a shared view, almost you know, it drives policy but it's also something which I think the whole of society needs to sort of think about how we address and what we want to do collectively. I wouldn't place it as a barrier but I would highlight it as a strength that we've had and I think we're hopeful that we'll continue is that long-term commitment in terms of government and the NHS and I think that's really powerful in this space to maintain the UK's position as being able to ask these questions and to show that leadership. Ana Lisa: And to bring together, we need to work really closely across the ecosystem. So in my mind one of the challenges is if one part is missing then that person is not going to get the treatment and how we keep joining up these really important dots across the whole ecosystem to make sure that most people will one day be able to get a treatment. Julia: And all those dots honestly, those dots can never even start unless you have a diagnosis and it's in time. And so there are so many people around the world working on each of those dots that connect a child or a patient to a treatment, but if you can't even be diagnosed or if you're diagnosed too late, which is what the reality is in the world of rare conditions right, then you know, then it's a little bit futile to race to a treatment or even think if that's possible. So I think the very, very first thing is: can we find children and patients, like can we find children like Mila in time? And I love hearing the word ‘hope' that's the word that keeps me going and doing what I'm doing because if there isn't any hope it's pretty hard to keep fighting, so I'm really glad, thank you both for having hope. Okay, we'll wrap up here. Thank you to Ana Lisa and to Rich for joining me in this conversation today as we shed some light on the challenges you know that those with rare conditions are facing. We touched on the work being carried out across the Genomics ecosystem in the UK to support those living with rare conditions. If you'd like to hear more of this, please subscribe to the G Word on your favourite podcast app. And thank you so much for listening. I've been your host, Julia Vitarello. This podcast was edited by Mark Kendrick at Ventoux Digital, and produced by Naimah Callachand.  

Episode 9 - Introducing Claire Coughlan, Clinical Lead for Bowel Cancer UK. Join us in this episode as Claire and Raphaela engage in insightful discussions surrounding crucial aspects of Stoma care. Disclaimer: Please note that all information and content on the UK Health Radio Network, all its radio broadcasts and podcasts are provided by the authors, producers, presenters and companies themselves and is only intended as additional information to your general knowledge. As a service to our listeners/readers our programs/content are for general information and entertainment only.  The UK Health Radio Network does not recommend, endorse, or object to the views, products or topics expressed or discussed by show hosts or their guests, authors and interviewees.  We suggest you always consult with your own professional – personal, medical, financial or legal advisor. So please do not delay or disregard any professional – personal, medical, financial or legal advice received due to something you have heard or read on the UK Health Radio Network.

Irish medics are sounding the alarm because scabies cases are on the upswing and are turning into a bit of a pesky public health conundrum. What's fuelling this itchy outbreak, and more importantly, how do we stop this scratchy situation from spreading? Tom Dunne was joined by Dr Scott Walkin, Clinical Lead in Infection Control and GP to discuss...

Moira Hannon speaks to 71-year-old Bobby Norris from Tallaght in Dublin, who suffered a stroke two years ago and Prof. Joseph Harbison, Clinical Lead, Irish National Audit of Stroke, discusses how Ireland fares when it comes to strokes.

This is a republishing of an archived episode with Karen Treisman.Dr Karen Treisman, MBE, is a Highly Specialist Clinical Psychologist and trauma specialist who has worked in the National Health System and children's social services for several years. Karen has also worked cross-culturally in both Africa and Asia with groups ranging from former child soldiers to survivors of the Rwandan Genocide. She also is the author of 11 books/workbooks, including the bestselling book, “The Therapeutic Treasure Box,” and of 5 sets of therapeutic card decks.Karen has extensive experience in the areas of trauma, parenting, adversity (ACE's) and attachment, and works clinically using a range of therapeutic approaches with families, systems, and children in or on the edge of care, unaccompanied asylum-seeking young people, and adopted children.Karen also specialises in supporting organisations and systems to move towards becoming, and to sustain adversity, culturally and, trauma-informed, infused, and responsive practice. This work focuses on creating meaningful and multi-layered cultural and paradigm shifts across whole systems. Karen was awarded a Winston Churchill Fellowship Travel Award which involved visiting several places in the USA to further study whole systems, and organisational approaches to trauma-informed and trauma-responsive care. This topic is also the focus of Dr Treisman's new books (2 volumes) entitled “A Treasure Box for Creating Trauma-Informed Organizations: A Ready-to-Use Resource For Trauma, Adversity, and Culturally Informed, Infused and Responsive Systems”In addition to holding a doctorate in Clinical Psychology, Karen has undergone a range of specialist training courses including in EMDR, Narrative Therapy, Narrative Exposure Therapy, Trauma-focused CBT, Dyadic Developmental Psychotherapy, Systemic Psychotherapy, Video Interaction Guidance, Sensory Approaches, and Theraplay.Karen has previously worked in both Milton Keynes's and Kensington and Chelsea's children-in-care and fostering services; and within the National Implementation Service for evidence-based interventions for looked-after children, children on the edge of care, and children in custody at the Michael Rutter Centre in the Maudsley Hospital; and as Clinical Lead for a court assessment and intensive intervention team for children on the edge of care and in proceedings in Islington.Karen is an external consultant, trainer, speaker, and assessor to a variety of UK and International local authorities/child welfare, health care teams, schools, charities, and organisations including Barnardos, PAC-UK, AdoptionPlus, BAAT, Pause, Action Trauma, Candle Trust, Grandparents Plus, Three Steps Ireland, MedicaCPD, and the Fostering Network. Karen is also an expert witness and regularly undergoes a variety of assessments for court. Additionally, Karen is also an associate editor for the Journal of Child and Adolescent Trauma and a reviewer for the Journal of Adoption and Fostering; and for several book publishers.Karen was also awarded the 2018 Psychology Professional of the Year Award for Excellence in Attachment and Trauma; Youth Psychology Professional of the Year 2020; and an MBE for Outstanding Services for Children. She is also on the Queens 2020 Honours list.In This EpisodeSafe Hands Thinking Minds WebsiteKaren's books on Amazon---What's new with The Trauma Therapist Project!The Trauma 5: gold nuggets from my 700+ interviewsThe Trauma Therapist Newsletter: a monthly resource of information and inspiration dedicated to trauma therapists.This show is part of the Spreaker Prime Network, if you are interested in advertising on this podcast, contact us at https://www.spreaker.com/show/5739761/advertisement