1. Medicine and medical research in thesustainable community Tim Chico Senior Clinical Lecturer/Consultant Cardiologist

2. Medicine and medical research in thesustainable community Tim Chico Senior Clinical Lecturer/Consultant Cardiologist 3. At some point in my life I expect to need medicaltreatmentA: yesB: no 4. From what you know of the NHS;A: I think it represents a sustainable model ofhealthcareB: I think it is an unsustainable model of healthcareC: Dont know 5. How many deaths in UK hospitals areavoidable?A: 1 in 10B: 1 in 20C: 1 in 50D: 1 in 100 6. What I would like you to think about The place of medicine in society; static, changing,improving? Whose responsibility is health? What is the right relationship between patient anddoctor? Do we need more medical research? Is use of animals justified for medical research? 7. I am studying a subject in;A: HumanitiesB: ScienceC: Other 8. Have you read a work of Shakespeares?A: yesB: no 9. Can you describe the Second Law of Thermodynamics?A: yesB: no 10. Have you read a work of Shakespeares AND can describe the Second Law of Thermodynamics?A: yesB: no 11. 1959: Scientists versusHumanities2013: Medics versus non-medics 12. What is a heart attack? 13. What is a heart attack?A) Sudden death or life-threatening event due to cardiac rhythm disturbanceB) Acute interruption of myocardial blood flow by rupture of an atherosclerotic plaque causing myocyte necrosis that can cause no symptoms 14. Human coronary angiograms of normal and occluded rightcoronary arteries 15. Should non-medics know more about medicine? 16. Should non-medics know more about medicine?Paternalistic, patronising: I knowwhats best for you 17. Should non-medics know more about medicine?No decision about me, without me. Open discussion of options, informed consentPaternalistic, patronising: I knowwhats best for you 18. Which doctor would you prefer?A) Paternalistic, patronising: I know whats best for youB) No decision about me, without me. Open discussion of options, informed consent 19. Youre admitted to hospital with a heart attack.How long do you think it would take to properly explain the diagnosis and treatment?A) 10minB) 30 minC) 1hrD) More than 1hr 20. You see a doctor who explains your illness andtreatment. How much information do you retainimmediately afterwards?A) 100%B) 75%C) 25%D) 10% 21. Imagine a disease that is fatal if untreated butcurable if found early. It affects 1 in 1000students. Doctors invent a test that is correct 95% of the time. You test positive.What is the chance you have the disease?A) 95%B) 50%C) 2%D) 0.01% 22. When a drug is prescribed for diabetes, what proportion of patients take at least 80% of the tablets they should?A) 100%B) 90%C) 66%D) 50% 23. How many years fewer do smokers live onaverageA) 20B) 10C) 7D) 3E) 1 24. Better understanding of medicine might help; Understand and evaluate care provided by medics Reduce personal risk of disease Influence public health in non-medical career paths Make informed political choices about health fundingand research 25. But how good is medicine anyway? 26. What is your current view of Medicine?A) Extremely advanced; surely there isnt much more we can achieve?B) Fairly advanced; we may be approaching a limit to what we can doC) Still quite a lot of room for improvements in treatment and understandingD) Primitive; people will look back on us in 20 years time and be stunned by how little we could do 27. A patient consults a doctor because of a symptom (for example pain). What percentageof such cases can currently be medically explained?A) 100%B) 90%C) 66%D) 50% 28. How do we know a treatment is effective?Anecdote (not very useful)Observational studies (lots of flaws)Randomised Controlled Trials (RCT); the best of a badbunch, but still lots of problems 29. A GP gives you a treatment. What is the likelihood that there is Randomised ControlledTrial evidence the treatment works?A) 100%B) 75%C) 50%D) 25% 30. 1922 31. 194219491983 2005 32. The current state of Medicine Amazing advances in the last 50 years Extremely expensive Still limited in what we can achieve Huge health inequalities These factors drive the need for more research 33. But do we need research? 34. Do you agree with Chris Boardman? A) Yes B) No C) Not sure 35. But do we need research? 36. Does medical research need to use animals? Most does not; health services research, studies inman, cell culture. Particularly good for observationalstudies. Some cardiovascular studies require use of animals,particularly those that change something (like agene) All medical therapies have passed through pre-clinical, i.e. animal studies 37. I would take a drug that had never been administered to an animal previously Yes; preclinical studies didnt pick up TGN1412 No; preclinical studies are imperfect but better thannothing 38. Regenerative medicine: growing neworgans 39. You have a heart attack, which kills 30% of theworking part of your heart. How muchimprovement can current medical treatment achieve?A) 100%B) 50%C) 20%D) 1% 40. Is it currently possible to grow a human heart from a single cell? Yes No 41. It is currently possible to grow a human heart from a single cell! We know this is possible; since we have all done itonce Regenerative medicine hopes to switch on andcontrol the existing pathways that made our organsin the first place 42. How can zebrafish tell us anything about ourselves? Conservation: higher organisms use/adapt existingprocesses The same genes that make blood vessels in zebrafishmake blood vessels in humans 43. Developing embryo 0-16h 44. Aortic coarctation is a congenital abnormality in bloodvessel formation 45. PTH1R mutations cause Blomstrand lethalchondrodysplasia Blomstrand, Pediatric Radiology 1985 46. Blomstrand lethal chondrodysplasia is associated withaortic coarctationReferenceSex Aortic CoarctationBlomstrand, Pediatric Radiology 1985F YESSpranger, Advances in human genetics 1995M Not knownYoung, J Med Genet 1993 F YESLeroy, Am J Med Genet 1996F YESLoshkajian, Am J Med Genet 1997 F YES MYESDen Hollander, Am J Med Genet 1997FNOFNot knownOostra, Am J Med Genet 1998 FNot knownGalera, Pediatric Radiology 1999 M NOOoostra, Virchows Arch 2000 FNO MYESFNO M NOHoogendam, Journal of Clin Endocrin & Met 2007 MYES 47. Research Questions 48. Research Questions Is PTHR1 needed for aortic formation? 49. Does PTHR1 directly contribute to aortic formation? 2d old control morphantembryo 50. Does PTHR1 directly contribute to aortic formation? 2d old control morphantembryo 51. Does PTHR1 directly contribute to aortic formation? 2d old PTHR1morphantembryo 52. Does PTHR1 directly contribute to aortic formation? 2d old PTHR1morphant Head embryo 53. Research Questions Does PTHR1 directly contribute to aorticformation? 54. Research Questions Does PTHR1 directly contribute to aorticformation? yes 55. Research Questions What is the nature of the aortic defect? 56. What is the nature of the aortic defect? 57. Research Questions Does PTHR1 directly contribute to aorticformation? yes What is the nature of the aortic defect causedby switching off PTHR1? a localised loss ofaorta 58. Research Questions How is this happening? 59. Notch signalling helps cells talk to each other 60. Notch signalling helps cells talk to each other 61. Green = Notch signallingNormal PTHR1 Site of future occlusionswitched off 62. If we switch on Notch signalling it rescues the aortic defect 63. What have we learned We know a little about why some babies withBlomstrands chodrodysplasia have aorticabnormalities We think this tells us that Notch is important inaortic formation generally Switching on Notch signalling might be a usefultherapy if we can find a way to do this 64. Summary Biomedical research is maddeningly slow, and anysingle study tells us hardly anything. However, if wewant to move forward, research is necessary If we discover, we understand. If we understand, wecan treat