PLME Science Curriculum

1. PLME Science Curriculum Julianne Ip, MD Associate Dean of Medicine (PLME and VIMS) Clinical Associate Professor of Family Medicine Alpert Medical School Brown University

2. How will we go from college freshmen

3. To MD graduates of the Alpert Medical School of Brown University 2012

4. Overload of facts and information, fatigue, loss of compassion and passion for learning, and humanity

5. HHMI-AAMC report • concerns about increasingly rapid rate at which new • knowledge revises our understanding of sciences • fundamental to medicine • Importance of educating future physicians to be • “inquisitive” • To help them build a strong scientific FOUNDATION… • but not overwhelm them with “facts” • To equip them with the knowledge, skills and habits to • integrate new scientific discovery into their medical • practice throughout their lives…

6. Brown’s Baccalaureate-MD program is poised to be a pilot for changes in pre-medical education. We set the admissions standards and competencies required for our curriculum.

7. The Warren Alpert Medical School of Brown University

8. Basically, assist and teach extremely bright, intelligent, motivated young men and women the skills and fuel their passion to be LIFE-LONG LEARNERS, to practice science-based medicine with greater synergy and efficiency along the continuum of their premedical and medical education.

9. PLME versus Standard Pre-Med PRE-MED Requirements PLME COMPETENCIES • Biology-three semesters (most place out of intro level so have 2 semesters) • Inorganic Chemistry-one semester • Organic Chemistry-one semester • Physics-2 semesters • Calculus-one semester (most place out) • Humanities/Social Science ( 2 writing courses) • No MCATS • Biology-2 semesters • Inorganic Chemistry-2 semesters • Organic Chemistry-2 semesters • Physics-2 semesters • Calculus-generally 1 semester minimum • English-2 semesters • MCATS

10. We start with our end product--our Brown MD graduate. What does it take? • Our graduates must be ready to be outstanding residents and future physicians therefore they must be outstanding 3rd- and 4th- year med students • Our first- and second-year med students must be prepared for clinical clerkships, clinical electives and decisions about future professional career • Therefore, our PLMEs must be prepared for first- and second-year integrated basic medical sciences and the Doctoring course

11. Two semester freshmen/sophomore course; integrate Chemistry, Physics, Math pertaining to biological and medical sciences Senior year one semester capstone course: interdisciplinary, integrative case-based promoting a holistic view of the human condition. Emphasis on: - Self-directed learning - Small group learning - Incorporation of ethics, history of medicine, new technology particularly as it pertains to the humanistic aspects of patient care Initial Proposal

12. PLME Science/Behavioral –Social Science and Humanities curriculum committee • Associate Dean of Medical Education • Director of First and Second year Basic Science Curriculum (eventually the second year assistant director took over) • A Cogut Fellow in the Humanities (funded by the Medical School to oversee the writing and development of the curriculum) • Associate Dean of the College (for sciences) • Associate Dean of Medicine (PLME)

13. Contributing Groups • PLME Alumni Survey and Focus Group • PLME advising deans • Alpert Medical School students survey and focus group • PLME survey and focus group • Wayland Collegium • College funded think tank group • Picks one topic/semester • Interdisciplinary: included physics, math, biostats, chemistry (both inorganic and organic) and biology faculty

14. CHALLENGES

15. Alpert Medical School takes ownership. Uses the HHMI-Scientific Foundations as template.

16. White Paper

17. PLME 1000 Senior Seminar inScientific Medicine • This course is an interdisciplinary and integrative science course that will supplement the preparation of both PLME and premedical students for the study of medicine in the 21st century. • The course will use a case-based approach to relevant and contemporary subjects in medicine and health care, such as biological systems and their interactions, mechanisms of intra- and intercellular communication, drug therapy optimization, and humanistic aspects of patient care. • This course is intended for seniors interested in attending medical school, but will preferentially enroll students in the PLME. This is an S/NC course.

18. Assessments • Quizzes 10% • You will be a given a brief, five question quiz prior to the beginning of lecture each week. The quizzes will be based on your reading assignment for the week. • Participation (class and small group) 10% • This class and the learning you will be doing are structured around small group problem-based learning and class discussion. We are looking for thoughtful contributions that refer directly to the readings and lectures at hand. • Reflective Narratives 20% • You will be asked to write three reflective narratives during the course. These narratives should be one page in length, single spaced and be in response to topics presented in the course. Prompts for these narratives will be given in class. The due dates of the narratives are: • October 15th • November 5th • December 3rd • Midterm Exam 25% • The midterm examination will mainly be comprised of single best answer, multiple choice questions but may also contain other questions types (true/false, fill in the blank and essay type questions). Questions on the midterm examination will be drawn from lecture, small group discussions, large group discussions and the readings. • Final Exam *same as midterm 35%

19. Teaching Assistants: • There are six teaching assistants for this course. Each student will be assigned one of these teaching assistants for small group work. • TA’s are second-year medical students with an interest in medical education; generally are participating in the Teaching Academy and Scholarly Concentration in Medical Education

20. First three weeks of course we start with sex… Objectives: Describe the molecular biology of androgen insensitivity.   Compare and contrast the phenotypic variation seen in androgen insensitivity.   Describe the medical management of differences of sex development. Construct an argument for the postponement of surgical management of differences of sex development using ethical principles.

21. Readings: • Jääskeläinen J. Molecular biology of androgen insensitivity.  Molecular and Cellular Endocrinology.  In press. • Wiesemann C, Ude-Koeller, Sinnecker GHG, Thyen U. Ethical principles and recommendations for the medical management of differences of sex development (DSD)/intersex in children and adolescents. Eur J Pediatr (2010) 169: 671–679. • Dreger, A; Chase, C; Souza, A; Gruppuso, P. Frader J: Changing the Nomenclature/Taxomony for Intersex; A Scientific and Clinical Rationale. J Ped Endocrinology and Metabolism 19 729-733 (2005) • Phornphutkul, C; Fausto-Sterling, A; Gruppsuo, P: Experience and Reason Pediatrics Vol 106 No1 135-137 2000 • Hines, M. Sex-related variation in human behavior and the brain Trends in Cognitive Science Vol 14 no. 10 448-456

22. Monday, September 10th: Session #1 Quiz on Readings (Ip; 10 minutes) Lecture on Androgen insensitivity (Gruppuso, 70 minutes) Wednesday, September 12th: Session #2 Case-based vignettes on diagnosis and treatment of androgen insensitivity (Forcier, 40 minutes)Discussion of the ethics of medical management of sex differentiation (Small Groups, 40 minutes)

23. S S P- -P P- -P SRC Complete Androgen Insensitivity (Testicular Feminization Syndrome) Mutation in AR gene affecting androgen binding to AR or AR binding to DNA. • X-linked recessive disorder, expressed in 46,XY individuals only • Mutation in the Androgen Receptor gene • Manifests as a disorder of sexual differentiation • Breast development and female habitus at puberty; primary amenorrhea; scant or absent pubic and axillary hair • Genitalia: female with blind vaginal pouch • Wolffian derivatives: usually absent • Mullerian derivatives: absent or vestigial • Gonads: testes

24. Target tissues 5a-dihydrotestosterone Steroid Hormone Biosynthesis 7-dehydrocholesterol cholesterol cortisol progesterone aldosterone androstenedioneestrone testosterone estradiol Gonads

25. Awareness of Gender Identity Between ages 1 and 2— Children become conscious of physical differences between sexes At 3 years old— Can label themselves as girl or boy By age 4 Gender identity is stable, for many/most Recognize that gender is constant

27. Small group discussion…TA Guru • What is sex? What is gender? Who defines them? • Are they binaries? • How much does culture play a role in gender? Does it at all? Are there differences across countries/regions? • Does sex determine gender? How much does nature play a role in gender? How about nurture? Greenspan seems to suggest at the end of the reading that androgens may play a role in gender identification—do you agree? • Where do individuals with DSD fall? • How much does gender define you? Is it a large part of your identity? Do you feel you fall into the gender binary? How do we understand individuals that don’t quite fit into the gender binary (ie tomboys)? Is there a stigma associated with not conforming to your culturally expected gender? Does it differ for males and females? (ie is it worse to be a feminine guy or a masculine girl? Does this influence how you think of DSD individuals or what you would recommend to them?

28. Week 2-Evidenced-based medicine; biostatistics learning the terms

29. Biostatistics: group problem solving • In a population of 1000 women, 250 are on tamoxifen to prevent breast cancer. 25 of the women on tamoxifen develop breast cancer. • Of the 750 women not on tamoxifen, 200 develop breast cancer. • What is the number needed to treat with tamoxifen to prevent one case of breast cancer? Risk of developing breast cancer on Tamoxifen: 25/250 Risk of developing breast cancer not on Tamoxifen: 200/750 Absolute risk reduction = 25/250 – 200/750 NNT = 1/ARR = 5.88 (round up to 6)

30. Breast Cancer Screening and Overview of Breast Cancer: Goals Review current guidelines for breast cancer screening, including screening of high risk patients with MRI Highlight controversy surrounding screening mammography Overview of the management of malignant breast diseases Identify who and how to screen for familial breast and gynecologic cancers

31. Mammography, when to start? • Sensitivity: 77%-95% • Specificity: 94%-97% • Seven statistical models showed screening mammography reduces the rate of death from breast cancer by 7 to 23 percent, with a median of 15 percent. • Meta-analysis of 8 randomized trials • Reduction of rate of death for women > 40 y • Reduction of mortality by 15 to 20% for ages 40 to 49 yr • Reduction of mortality by 16 to 35% for ages 50 to 69 yr • NB: Results reported for women ‘invited to screen’. Advocates suggest women ‘actually screened’ probably benefit even more.

32. Standard Mammography views;Cranio-caudal and Midline Oblique

33. Screening Guidelines • In USA, most recommend screening at 40 years • Between 40-49 years: • ACS: annually • ACR: annually • ACOG: every 1-2 years • NCI: every 1-2 years • USP-STF (2009): not recommended • Canadian Task Force on Preventive Health Care: not recommended • Annual screening > 50 years: • Most organizations • USP-STF (2009): every 1-2 years

34. Sample Midterm Multiple Choice Question Choose single best answer; bubble into scantron sheet • A new patient, a 28 year old single female comes to your office for a first time physical. She is otherwise healthy and has no risk factors for any illness including a negative family history for cancer, cardiovascular disease, hypertension or any other major illness. She asks you about her chances of developing breast cancer over her lifetime. You tell her that: • A:Every patient is different so you cannot answer • B:One in eight women will develop breast cancer • C:One in every one hundred women has breast cancer • D:Given she has no risk factors she will not develop breast cancer

35. Narrative Reflection Prompts • You are a primary care physician who is part of the new system of "capitation" on your group practice mandated by the changes after the election of 2012 in the "New" Affordable Health Plan. This capitation is similar to the United Kingdom system of having a set amount of funds to care for all your patients; so no matter what tests, procedures or exams you perform on your panel of patients, this is ALL the funds you will have. You receive $1,000,000 for the care of your 2500 patient panel, all ages. • One of your patients is a 27 year man who gets convicted of first degree murder and is incarcerated for life (no parole).  He needs a liver transplant. This transplant will cost $350,000 of your funds which will leave far less to care for the rest of your patients. Do you put the patient on the transplant list? Why or why not? • What if you have an active 80 year old who is still functioning at full capacity; he volunteers at the local school tutoring science and works out by running 1 mile per day. He has a wife who is healthy and 3 healthy children and 4 grandchildren who he often takes care of on a regular basis.  He needs a liver transplant. This will cost $350,000 of your funds as well.  Do you put him on the transplant list? Why or why not? • What if you had to CHOOSE between the two patients (given your limited funding)...how might you make this decision? If you HAD to choose one person, which would you choose and why?

36. Chronic Renal Disease Renal Transplantation Autism and Vaccines Pharmacology and Toxicology Prostate Cancer Clinical Arts and Humanities Health Care Financing: US and International

37. Next Steps Goals for the Redesigned PLME Year 1 Courses • Focus on the scientific competencies as detailed in the AAMC-HHMI report. • Develop interdisciplinary science courses that more effectively engage students interested in a career in medicine. • Integrate the sciences and non-science disciplines. An example is the incorporation of ethics or history of science into any discussion of new technologies.  Another example is an emphasis on the humanistic aspects of patient care whenever discussing application of new knowledge or technology. • Incorporate an inquiry-based approach into premed education. • Enhance the ability of all PLME’s to succeed in medical school, but especially members of underrepresented groups. Members of underrepresented groups typically fare worse in the courses listed above. The integrated courses will include periodic exams and regularly scheduled tutorials for students who need help.

38. PLME Freshman CourseSample Teaching Module Overall Strategy: Central topic, a young boy with hereditary fructose intolerance, a disorder of fructose metabolism that results from a mutation in the gene that encodes the enzyme, Aldolase B. The proposed strategy is to use this case study as a means to address basic concepts in quantitative reasoning, physics and chemistry through an emphasis on enzyme catalysis.

39. Case Presentation: Danny, a 3 year old boy was brought in for evaluation of failure to thrive (poor growth and weight gain).  His medical history included a profound aversion for sweet foods. In fact, it was described that he would retch when offered candy, other sweets, fruit juice, or fruit. Once, after drinking fruit juice, he vomited and had a near loss of consciousness for a short period of time. Based on this history, a it was suspected that Danny had hereditary fructose intolerance. This is a disorder that is inherited because it is due to a mutation in an enzyme. The enzyme, aldolase B, is involved in the metabolism of the dietary sugar, fructose. To confirm the diagnosis, Danny was admitted to the hospital and given an oral fructose load. During the test, he became sleepy and had a low blood sugar. Laboratory tests confirmed the diagnosis.

40. Background Biology What is fructose? (Discuss the major nutrients - carbohydrate, protein and fat - and the major dietary carbohydrates - glucose, fructose, sucrose, galactose and lactose) What is an enzyme? (Discuss the concept of catalysis) What is a mutation? (Review the central paradigm: DNA to RNA to protein)

41. Working with the Inorganic and Organic Chemists particularly as the material relates to biochemistry…how much do the students “need?” Chemistry as “gatekeepers” to medical school? Links to Important Principles in Chemistry and Physics:Chemistry Principles involved (pending review)Organic Molecule Structure (connectivity, shape, conformation - e.g., why are glucose and galactose different molecules? Can they interconvert? What about fructose and glucose?) Metabolism = chemical reactions of nutrients Kinetics - why are the adverse effects short lived as opposed to permanent?

42. Working with the General Physics professors on these cases. How much is “enough?” Their opinion or ours? Physics principles involved (pending review)Coulomb’s law Electric fields and potentials Electric dipoles Dielectrics and solubility Torque Newton’s Laws Energy Conservation

43. Work in Progress…Questions??? Thank you