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STIRRHS Seminar on Transdisciplinarity

STIRRHS Seminar on Transdisciplinarity. Dr William D. Fraser MD, MSc, FRCSC June 2 nd , 2006. Agenda. Oxidative Stress INTAPP Trial MIROS Program. Hypertension and pregnancy. Gestational hypertension Majority high-risk antenatal visits : high BP

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STIRRHS Seminar on Transdisciplinarity

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  1. STIRRHS Seminar on Transdisciplinarity Dr William D. Fraser MD, MSc, FRCSC June 2nd, 2006

  2. Agenda Oxidative Stress INTAPP Trial MIROS Program

  3. Hypertension and pregnancy • Gestational hypertension • Majority high-risk antenatal visits : high BP (24% of antenatal hospital admissions) • Ranked first among the direct obstetric causes of maternal death • Perinatal deaths (preterm delivery & intrauterine growth restriction) • 10 to 25% of all very low birth weight infants • Preeclampsia, or proteinuric gestational hypertension • Accounts for 1/3 of maternal deaths in pregnancy • Eclampsia • 20% occur without antecedent proteinuria Delivery is the only known cure of Preeclampsia

  4. Prevention of preeclampsia?

  5. Definition of Oxidative Stress • A disturbance in the prooxidant-antioxidant balance in favor of prooxidants leading to potential damage. Sies, 1991

  6. Oxidative Stress: Reactive Oxygen and Nitrogen Species Reactive nitrogen species Nitric oxide, NO• Nitrogen dioxide, NO2• Reactive oxygen species Superoxide, O2•- Hydroxyl, OH• Peroxyl, RO2• Alkoxyl, RO• Hydroperoxyl, HO2•

  7. Antioxidants of Interest • Carotenoids • Xanthophylls • Metallothionein • Coenzyme Q10 • Uric acid • Flavonoids & Polyphenols • Herbal remedies such as theaflavin, Ginko biloba, etc. • Vitamin E (Tocopherol) • Vitamin C (Ascorbic Acid) • Vitamin A • Proteins: • Superoxide dismutase • Glutathione peroxidase • Catalase • Ceruloplasmin • Beta-carotene

  8. Oxidative Stress/ Abnormal Lipid Metabolism / Endothelial Dysfunction /Preeclampsia

  9. Antioxidants

  10. Antioxidants in the Prevention of Preeclampsia Primary Outcome Measure Mean PAI-1/PAI-2 during gestation in completed-study cohort 0.50 0.45 0.40 0.35 0.30 0.25 0.20 Placebo (n = 82) Vitamins (n = 79) 12 16 20 24 28 32 36 40 Chappell et coll., Lancet, 1999

  11. Secondary Outcome Measure: Frequency of Preeclampsia 1512 Women Screened by uterine Doppler 284 Randomised Women with High Risk of Preeclampsia 142 Placebo Total Preeclampsia 24 (17%) 141 Vit C & E Total Preeclampsia 11 (8%) Relative Risk: 0.39; 95% CI 0.17-0.90

  12. INTAPP Protocol review and study design

  13. Primary Hypotheses • Oral antenatal supplementation with vitamins C and E reduces the incidence of "Gestational hypertension (with or without proteinuria) and its adverse condition(s)"

  14. Population • Stratum I: Nulliparous women without additional identified risk factors • Stratum II: Nulliparous and multiparous women with identified risk factors

  15. Inclusion criteria • Women between 120/7 and 186/7 weeks of pregnancy • Gestational age of patients will be based on the last menstrual period and confirmed by early ultrasound examination. (if discrepancy > 7 days, use ultrasound to estimate gestational age) • At least 18 years old • Speak a language known by the medical staff • Plan to deliver in a participating centre

  16. Definition of the Primary Outcome Gestational hypertension (with or without proteinuria) and its adverse condition(s) Gestational hypertension • Two or more readings of diastolic blood pressure  90 mmHg taken 4 hours apart within a 24-hour period and occurring after 20 weeks of pregnancy Severe gestational hypertension • Two recordings of diastolic blood pressure of 110 mmHg or systolic pressure 160 mmHg at least 4 hours apart within a 24 hour period Proteinuria • Excretion of > 300 mg protein in 24 hours Based on a modification of Canadian Consensus statement definition and ACOG criteria

  17. Must include 1 or more of the following selected medical conditions: • Diastolic pressure ≥ 110 mmHg or systolic pressure ≥ 160 mmHg • Proteinuria > 3 g/24h urine collection • Convulsion (eclampsia) • Thrombocytopenia • Elevated liver enzyme levels (AST or ALT >70 U/L) • Creatinine > 180 µmol/L • Hematocrit < 24 and blood transfusion • IUGR <3rd centile • Perinatal death

  18. Participant Stratification

  19. Treatment Plan

  20. INTAPP Schematic design

  21. Procedures

  22. INTAPP a multidisciplinary team

  23. Organisation of sites

  24. Central Laboratory Aim of this procedure • Ensure appropriate processing, storing and shipping of blood samples in order to be able to perform sensitive analyses of vitamin C & E • Ensure an efficient system of communication between study sites, CL, GEREQ and the Center for Research and Evaluation in Diagnostics. • Testing of Vitamins C & E • Biological Specimen Bank

  25. Central Laboratory • At reception of your samples, CL will make an inventory of the samples, using a bar code scanner to ensure that content match the Inventory log • This will automatically creates a record in the MGS system at CL. • MGS will then store the following information: • Date and time of reception • Volume of samples • Quality of samples (intact and frozen)

  26. Specimen management system (PIERCE SYSTEM) • Andrew Grant Centre for Research & Evaluation in Diagnostics (CRED) Specimen Management System Université de Sherbrooke

  27. Management of blood specimens and vitamin E & C testing

  28. Food Frequency Questionnaire (FFQ) • Canada Bryna Shatenstein, PhD Montreal Geriatric Institute • Mexico Maria-Soccoro Parra, PhD National Institute of Public Health • China Baoquing Mo, PhD Nanjing Medical University

  29. J.R. Carlson Laboratories inc Timothy Johaneck Robert Meyer • Study medication kit preparation • Shipment to study sites

  30. Study sites 42 study sites - Canada 21 - Mexico 10 - China 4 - Argentina 7 Canada Belgium China Mexico Argentina

  31. Maternal and Infant Research on Oxidative Stress

  32. INTAPP-MIROS Synergy

  33. MIROS Synergy among projects

  34. MIROS-INTAPP Parallel Structures

  35. MIROS Organizational Structure

  36. Committees Members

  37. CommunicationStrategy

  38. Thank you !

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