Gideon Koren

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Gideon Koren M.D., FACMT, FRCP(C) (born 1947 in Tel Aviv) is a Canadian pediatrician, clinical pharmacologist, and toxicologist. Koren is also a noted composer of Israeli popular music.

Biography

Early life and academic background

Born in 1947 in Tel Aviv in the British Mandate of Palestine,just prior to the establishment of the State of Israel,Gideon Koren was raised in the neighbouring little town of Kiryat Ono.His father was the chief engineer of Reading Power station of the Electricity Company in Tel Aviv. In his childhood he played French horn in the orchestra of the premilitary youth Gadna. Koren received his Doctor of Medicine from the Sackler School of Medicine at Tel Aviv University in 1973. After a period of military service, he pursued postgraduate clinical studies in pediatrics and pediatric nephrology, and research training in pediatric toxicology and pharmacology and membrane biology at The Hospital for Sick Children and the University of Toronto. He joined the staff of the University and Hospital and rose rapidly through the ranks to full professorship in pediatrics, pharmacology and medicine, won a Career Scientist Award from the Ontario Ministry of Health and established an international reputation as an expert in the field of clinical pharmacology and toxicology. He had a role in a controversial hospital dispute.[1] He was later awarded the endowed Ivey Chair in Molecular Toxicology at the Schulich School of Medicine at The University of Western Ontario. At UWO, he heads the establishment of a National program in human toxicology in parallel to his continuing work at the University of Toronto and the Hospital for Sick Children.[2]

Arts background

In parallel to his academic career, Gideon Koren is an established, award-winning composer and author. In 1971, while studying medicine at TAU, Gideon “Gidi” Koren founded the Israeli musical group, “The Brothers and the Sisters” (ha'achim veha'achayot). Koren’s songs and the group’s unique Israeli folk/country style put them at the top of the charts and of Israel’s popular annual song competitions for over a decade. The band performed many of Gideon Koren’s classic songs and musical plays for children.[3]

In 1974, in collaboration with Israeli superstar Shlomo Artzi, Koren composed a record album based on his grandmother Keri's story, A Journey to Noteland, introducing the world of music to children. A musical based on the book and CD of A Journey to Noteland had its stage debut in Israel in 2008 and continues to be performed for elementary school children throughout the country.[4]

In 1992 he founded the Bear Theatre at the Hospital for Sick Children in Toronto, the only such theatre worldwide where health professionals perform weekly for hospitalized children and their families. The musical "Tails" — script, songs, direction and children's book by Koren — has served as a model for other hospitals. In July 2007 the theatre celebrated 15 years and 750 shows.[5] At the hospital, Koren goes by the nickname "Gidi" and takes pride in wearing eccentric hats to the performances of "Tails."

In 2004, Koren's band, “The Brothers and the Sisters” reunited by popular demand with the composer’s active support. In 2005, they toured North America following the publication of a commemorative Hebrew-English book of the beloved Israeli poet Natan Yonatan’s poetry accompanied by a CD of his songs set to music by Koren and performed by the band.[6] Since then “The Brothers and the Sisters” have continued to appear throughout Israel in programs featuring Koren’s hit songs, many of which were written to the words of Israel’s foremost poets: Yehudah Amichai, Leah Goldberg, Rachel, Natan Yonatan, Amir Gilboa, Ze’ev Jabotinsky and others. In 2008, NMC released a double CD and documentary booklet of 44 of the band’s favorites. 42 of these songs had music and/or lyrics and arrangements by Koren, as well as his participation as musician in early recorded accompaniments. Celebrating this collection and the band’s comeback, Israel’s Channel One dedicated a one hour holiday TV special to “The Brothers and the Sisters”, who performed old favorites and new songs by Gidi Koren.[7]

Professional contributions

Gideon Koren is a pediatrician, pharmacologist and toxicologist at the University of Toronto and the University of Western Ontario. He is Professor of Pediatrics, Pharmacology, Pharmacy and Medical Genetics at the University of Toronto, and Professor of Medicine, Pediatrics, and Physiology-Pharmacology at the Schulich School of Medicine of the University of Western Ontario.

In 1985, Gideon Koren founded the Toronto Hospital for Sick Children's Motherisk Program, which he continues to direct. Motherisk counsels women, their families and health professionals on the safety-risks of drugs, chemicals, radiation and infections during pregnancy and lactation. Motherisk counselors talk to hundreds of women and their healthcare providers each day.[8]

Since 1986, Koren has trained physicians from over 30 countries, and over 80 graduate students in pharmacology, making his program the largest worldwide.[9]

Gideon Koren has been a Senior Scientist of the Canadian Institutes of Health Research (CIHR) .[10] In 2004, Koren was appointed by the National Institutes of Health (NIH) of the United States Department of Health and Human Services as the inaugural chairperson of the Steering Committee for the newly created Obstetric-Fetal Pharmacology Research Unit (OPRU) Network.[11] Since 2005, Koren has been the Course Director of the Annual Summer Institute in Maternal-Fetal Pharmacology, a collaboration between the National Institutes of Health and Canadian Institutes of Health Research.[12]

Research

The research group headed by Koren at The University of Toronto and the Hospital for Sick Children[8] is studying the fetal effects of drugs and chemicals, as well the effects of medications and toxins in infants and children.

Koren's research in maternal – fetal and pediatric pharmacology and toxicology has focused on understanding the complex interactions between drugs, both illicit and medicinal, and the developing human being. These include the effects of drugs taken by the mother on her unborn baby, the role of the placenta in modulating fetal damage, and the way babies and children handle drugs. Koren and his colleagues use research approaches ranging from those of molecular and cell biology to whole-body pharmacokinetic or dynamic experiments and population studies. They collaborate with specialists in the field of psychology in order to measure the neurobehavioural effects of drugs on infants and children.[13]

Together with colleagues at the University of Western Ontario, Gideon Koren is studying Ecological System Toxicology with a focus on the health risks to aboriginal Canadians residing near oil refineries in Western Ontario.

FASD focus

Gideon Koren is the founder of the FACE (Fetal Alcohol Canadian Expertise) Network[14] and founding editor of the peer reviewed Journal of FAS International (Fetal Alcohol Syndrome).[15] At the forefront of FASD (Fetal Alcohol Spectrum Disorder) research and the development of screening and diagnostic techniques,[16] he is also committed to outreach to medical professionals and community workers in the Northwest Territories and around the globe, both in person and through the electronic media.[17][18]

Publications

Gideon Koren is a reviewer and editor for leading journals and has published over 1000 peer review articles[19] and 15 medical books,[20] among them:

  • Retinoids in Clinical Practice: The Risk-Benefit Ratio (Medical Toxicology). New York: M. Dekker, 1993. (ISBN 0824787781)
  • The Children of Neverland: The Silent Human Disaster. Toronto: Kid in Us, 1997. (ISBN 0968180108)
  • The Complete Guide to Everyday Risks in Pregnancy & Breastfeeding: Answers to Your Questions About Morning Sickness, Medications, Herbs, Diseases, Chemical Exposures & More. Toronto: R. Rose, 2004. (ISBN 0-7788-0084-9)
  • Medication Safety in Pregnancy and Breastfeeding. New York: McGraw-Hill, Health Professions Division, 2007. (ISBN 0071448284)
  • Medication Safety in Pregnancy and Breastfeeding: The Evidence-Based, A to Z Clinician's Pocket Guide. New York: McGraw-Hill Medical, 2007. (ISBN 0071448276)

Notable achievements

Preventing renal damage

Koren has found a way to prevent severe kidney damage caused by the cancer drug ifosfamide by using the antidote n-acetyl cysteine. The drug ifosfamide can save the lives of children with certain cancers, but often at the grim price of damaging the kidneys. Koren’s discovery may save the kidney and have a major impact on the lives of these children.[21]

Codeine during breastfeeding

Koren described a breastfed infant who died from opioid toxicity following the use of codeine by his mother. This was the first described death of an infant by a drug in breastfeeding, secondary to the genetic predisposition of the mother to produce more morphine from codeine. Further research by his group has shown that this is not a rare phenomenon.[22]

FAEE

Using the baby’s first bowel movement (meconium), Koren’s group showed that, by measuring a by-product of alcohol (FAEE), they could detect objectively babies exposed to excessive maternal drinking in pregnancy.[23]

Folic acid

Koren’s group has shown that the fortification of flour with folic acid in Canada has resulted in a dramatic decrease in neuroblastoma, an early and very dangerous cancer in young children.[24]

Drugs in pregnancy

Through over 500 research papers on drugs in pregnancy, Koren has identified drugs and chemicals that are damaging to the fetus (e.g., organic solvents, corticosteroids, lithium, misoprostol), and those that are safe to take (e.g., paxil, calcium channel blockers, prozac).[25]

Nausea and vomiting in pregnancy (NVP)

In a landmark paper, Koren analyzed the estimated cost and actual burden to society caused by nausea with and without vomiting among the pregnant woman associated with the Hospital for Sick Children's Motherisk program.[26] Another study of NVP conducted by the research group at Motherisk addressed the effects of nausea and vomiting of pregnancy and its treatment with diclectin on child neurodevelopment. The conclusion, published in The Journal of Pediatrics in April 2009, states that "NVP has an enhancing effect on later child outcome. Diclectin does not appear to adversely affect fetal brain development and can be used to control NVP when clinically indicated."[27]

Long-term safety

Koren established the only group worldwide that systematically studies brain development in children exposed in utero to drugs. The group has tested IQ, language, attention and behavior in children exposed during pregnancy to antidepressants, cocaine, cyclosporine, antiepileptics, and many other drugs.[28]

Neonatal pain

Koren and his group documented in 1997, for the first time, that neonates remember the pain of circumcision 6 months later, as evidenced by enhanced response to vaccination. This has been marked as a breakthrough in the understanding of the long term effects of early pain.[29]

Drugs that can kill toddlers

Koren established, for the first time, a list of drugs that can kill a toddler even with only one adult tablet. These drugs need to be acknowledged by physicians because toddlers often accidentally consume adult medication.[30]

Publication bias

Koren’s group has pioneered the research into sources of misinformation and bias in information given to pregnant women, misinformation which leads many of them to avoid treatment even for life-threatening conditions. This has led to major changes in the methods of counseling pregnant women.[31]

Hair analysis

Koren’s laboratory pioneered the use of neonatal hair to show exposure to drugs of abuse in pregnancy. Drugs such as cocaine, methamphetamine, heroin, etc., accumulate in the neonatal hair during its growth and hence serve as a long term “memory” of what happened during fetal life. This method has revolutionized the diagnosis of in utero exposure to drugs.[32] Koren's research in this area has also led to a new biological marker that can be used to help prevent heart attacks, measuring chronic stress over time.[33]

Deferiprone controversy

In 1996, a controversy erupted with regard to the safety and effectiveness of deferiprone. Koren believed the drug was effective for certain patients.[34] Olivieri of Toronto believed the drug was unsafe and ineffective.[35] Following the initial controversy surrounding this drug trial in Toronto, Koren sent five anonymous harassing letters to colleagues and later denied having done so.[36] Two independent inquiries by the CAUT and CPSO found that Koren had lied about sending the anonymous letters and only admitted guilt when confronted with DNA evidence against him.[37][38] Both also found academic misconduct with respect to the way in which he published the research article cited above on the safety and effectiveness of deferiprone. CAUT accepted "the parties’ submissions that this misconduct should not be represented as fraudulent" and further remarked that "It was the behaviour that preceded the research misconduct that the Committee found most unsettling." Spokesperson for the University of Toronto, Professor David Naylor, current president of the University and then Dean of the Faculty of Medicine and Vice Provost for Relations with Health Care Institutions, and others went on record regarding Olivieri's having "advanced 'demonstrably incorrect' allegations against others" and having used “hundreds of thousands of dollars of legal fees and services” from teachers' union funds, and then being “unable to admit she made a mistake....”[39][40][41] Prof. Naylor also went on record citing the bias of CAUT and its Inquiry as having favored Olivieri and her Union and pointing to the lack of independence of both committees.[42] While Olivieri was admired in some circles for defending academic freedom when news of the controversy first broke, others continue to question her publicity-seeking, concerned that Olivieri was wrongly placed on a pedestal during the deferiprone controversy and that her science was wrong.[43] Cumulative worldwide experience has confirmed Koren's position on deferiprone, indicating that deferiprone is safe and effective for some patients.[44] As a direct result of Nancy Olivieri’s public media campaign, approval for the medication was stalled,[45] meaning that North American children continued to be denied a medication which had since been approved around the world in dozens of countries[46] and could be the only hope for survival for some children.[47][48][49][50][51]

FDA Approval for Deferiprone

Finally, on October 14, 2011, "the U.S. Food and Drug Administration approved Ferriprox (deferiprone) to treat patients with iron overload due to blood transfusions in patients with thalassemia, a genetic blood disorder that causes anemia, who had an inadequate response to prior chelation therapy... The therapy is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug’s clinical benefit. The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients...."[52]

The wisdom of the FDA's accelerated (Fast Track) approval of deferiprone, was scrutinized in Dr Sidney Wolfe’s (PUBLICCITIZEN) letter (Oct. 12, 2011), to the FDA where he concludes, “…given the lack of data from adequate and well-controlled clinical trials demonstrating the safety and efficacy of deferiprone, as well as serious questions raised by DSl's inspection of study LA01 regarding the integrity of clinical trial data presented to the FDA by the sponsor, we urge the FDA to reject approval of NDA #021825 for deferiprone…….FDA approval of deferiprone based on such inadequate data would indeed set a recklessly dangerous precedent for drugs reviewed under an accelerated approval process in the future”.[53]

The FDA briefing notes associated with the decision reveal that the request for regular or normal approval for marketing of deferiprone was declined by the FDA following scientific review because the evidence presented in the Apotex New Drug Application failed to adequately demonstrate safety and efficacy. Also the FDA site inspection of Olivieri’s trials showed that Apotex had omitted or misrepresented 45% of the Olivieri data in its submission to FDA.

FDA then informed Apotex that additional satisfactory randomized controlled evidence and a full, detailed audit of the Olivieri trials were required if Apotex was to pursue regular approval. The company declined and pursued 'accelerated' approval (known as conditional approval in Canada and other jurisdictions), which requires the lowest level of evidence, in order to at long last make this drug available to the population with no other recourse. According to the FDA, "Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases."[54]

The US FDA "accelerated approval" for last resort treatment with deferiprone was based on a single arm, non-controlled, non-randomized retrospective re-analysis of 264 patients selected from 746 patients in pooled data from studies previously conducted, showing a 20% reduction in serum ferritin in 52% of patients, the clinical significance of which is uncertain. While the Advisory Committee document cited above also includes the statement that there was "a lack of data to verify absence of a mortality disadvantage when deferiprone is used over a long period of time", the disclaimer that opens this document clarifies as follows: "The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office." The further studies to which the company must commit as part of accelerated approval are not yet described.[55][56]

Awards and distinctions

  • Ontario Ministry of Health Career Scientist, 1986
  • Research Institute Distinguished Service Award, 1993
  • American Society of Clinical Pharmacology and Therapeutics Rawls-Palmer Progress in Medicine Award, 1997
  • Canadian Society for Clinical Pharmacology Senior Investigator Award, 1999
  • International Association of Therapeutic Drug Monitoring Irving Sunshine Award for Outstanding Contributions to Clinical Toxicology, 1999
  • Medical Research Council of Canada Senior Investigator Award, 2000
  • Canadian Society for Clinical Pharmacology Distinguished Achievement Award, 2002
  • International Association of Therapeutic Drug Monitoring Pippenger Award for Outstanding Contributions to Clinical Toxicology, 2003
  • Spirit of the Community Humanitarian Award, Toronto, 2007
  • Distinguished Scientist, Canadian Society for Clinical Investigation, 2010
  • The Poulsson Medal for 2011, given by the Norwegian Society for Pharmacology and Toxicology, presented to Gideon Koren in recognition of his outstanding scientific contributions in the area of drug safety during pregnancy. This is the first time the award has been given to a Canadian scientist.
  • Sumner J. Yaffe Lifetime Achievement Award in Pediatric Pharmacology and Therapeutics, Pediatric Pharmacy Advocacy Group, 2012
  • CIHR/CMAJ Top Achievements in Health Research Award: for revolutionizing the area of medication safety in pregnancy, 2011[57]

Currently held positions

Selected list of currently held positions (2010):[58]

  • Founder and Director, Motherisk Program, Hospital for Sick Children
  • Ivey Chair in Molecular Toxicology, University of Western Ontario
  • Holder, The Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation, Hospital for Sick Children
  • Founder and Head, Fetal Alcohol Canadian Expertise (FACE)[59]
  • Chair, Steering Committee, Breaking the Cycle, Toronto[60]
  • Editor in Chief (North America), Therapeutic Drug Monitoring[61]
  • Editor in Chief, Fetal Alcohol Research (FAR)[62]
  • Director of Research, The Canadian Foundation on Fetal Alcohol Research (CFFAR), 2008–present[63]
  • Director, Playwright and Producer of Tails in the Bear Theatre (Hospital for Sick Children)1992–present[64]

References

  1. ↑ Gatehouse, Jonathon, Maclean’s Magazine, Toronto, May 4, 2005. http://www.macleans.ca/culture/entertainment/article.jsp?content=20050509_105255_105255 Committee summary. http://www.cpso.on.ca/Publications/Discsum/2004/discmay04.htm#Koren
  2. ↑ Schulich School of Medicine & Dentistry Awards
  3. ↑ Examples of Dr. Gideon Koren's classic recordings for children http://www.israel-music.com/gidi_koren http://www.israel-music.com/dahlia_friedland/tales_shubi_dubi/ http://www.judaicawebstore.com/ProductInfo.aspx?productid=VT-32102
  4. ↑ Debut of the musical, A Journey to Noteland http://www.mouse.co.il/CM.articles_item,1022,209,28700,.aspx
  5. ↑ Porter, Miriam, Reassuring message helps young patients, Weekend Living Section, p.L6, The Toronto Star, July 28, 2007. http://www.thestar.com/living/article/239323 http://www.thestar.com/fpLarge/photo/239948 http://www.sickkids.ca/tails
  6. ↑ Within the Song to Live ISBN 965-229-345-8 http://www.bros-and-sis.com/images/press_natanyonatan1.jpg http://www.bros-and-sis.com/album_lihyot.shtml
  7. ↑ Gideon "Gidi" Koren and The Brothers and the Sisters http://www.bros-and-sis.com
  8. ↑ 8.0 8.1 The Hospital for Sick Children - Motherisk
  9. ↑ Koren G, Macleod SM: The state of pediatric clinical pharmacology;an international survey of training programs, Clin. Pharm Ther 1989;46:489-93.
  10. ↑ Project Information: Dr. Gideon Koren - CIHR
  11. ↑ Obstetric-Fetal Pharmacology Research Unit (OPRU) Network
  12. ↑ http://www.cihr-irsc.gc.ca/e/30158.html http://www.circlesolutions.com/summerinstitutes/index.cfm
  13. ↑ The Hospital for Sick Children Research Institute, Annual Report 2002.
  14. ↑ FASD Webcast
  15. ↑ The Hospital for Sick Children - Motherisk
  16. ↑ Gareri J, Chan D, Klein J, Koren G (January 2005). "Screening for fetal alcohol spectrum disorder". Canadian Family Physician 51 (1): 33–4. PMC 1479571. PMID 15732218. 
  17. ↑ NWT Health and Social Services - Programs and Services - Fetal Alcohol Spectrum Disorder (FASD) - Recent initiatives and key events supported by the Department
  18. ↑ Koren G, Nulman I, Chudley AE, Loocke C (November 2003). "Fetal alcohol spectrum disorder". CMAJ 169 (11): 1181–5. PMC 264960. PMID 14638655. 
  19. ↑ Koren G. at http://www.ncbi.nlm.nih.gov/entrez/query
  20. ↑ The Hospital for Sick Children - Motherisk
  21. ↑ Chen N, Aleksa K, Woodland C, Rieder M, Koren G (April 2008). "N-Acetylcysteine prevents ifosfamide-induced nephrotoxicity in rats". British Journal of Pharmacology 153 (7): 1364–72. doi:10.1038/bjp.2008.15. PMC 2437918. PMID 18278066. 
  22. ↑ Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (August 2006). "Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother". Lancet 368 (9536): 704. doi:10.1016/S0140-6736(06)69255-6. PMID 16920476. 
  23. ↑ Chan D, Knie B, Boskovic R, Koren G (July 2004). "Placental handling of fatty acid ethyl esters: perfusion and subcellular studies". The Journal of Pharmacology and Experimental Therapeutics 310 (1): 75–82. doi:10.1124/jpet.104.066597. PMID 15004219. 
  24. ↑ French AE, Grant R, Weitzman S, et al. (September 2003). "Folic acid food fortification is associated with a decline in neuroblastoma". Clinical Pharmacology and Therapeutics 74 (3): 288–94. doi:10.1016/S0009-9236(03)00200-5. PMID 12966372. 
  25. ↑ Koren G, Pastuszak A, Ito S (April 1998). "Drugs in pregnancy". The New England Journal of Medicine 338 (16): 1128–37. doi:10.1056/NEJM199804163381607. PMID 9545362. 
  26. ↑ Piwko C, Ungar WJ, Einarson TR, Wolpin J, Koren G (April 2007). "The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program". Current Medical Research and Opinion 23 (4): 833–40. doi:10.1185/030079907X178739. PMID 17407640. 
  27. ↑ Nulman I, Rovet J, Barrera M, Knittel-Keren D, Feldman BM, Koren G (July 2009). "Long-term neurodevelopment of children exposed to maternal nausea and vomiting of pregnancy and diclectin". The Journal of Pediatrics 155 (1): 45–50, 50.e1–2. doi:10.1016/j.jpeds.2009.02.005. PMID 19394042. Lay summary – Toronto Sun (April 23, 2009). 
  28. ↑ Nulman I, Rovet J, Stewart DE, et al. (January 1997). "Neurodevelopment of children exposed in utero to antidepressant drugs". The New England Journal of Medicine 336 (4): 258–62. doi:10.1056/NEJM199701233360404. PMID 8995088. 
  29. ↑ Taddio A, Katz J, Ilersich AL, Koren G (March 1997). "Effect of neonatal circumcision on pain response during subsequent routine vaccination". Lancet 349 (9052): 599–603. doi:10.1016/S0140-6736(96)10316-0. PMID 9057731. 
  30. ↑ Koren G (1993). "Medications which can kill a toddler with one tablet or teaspoonful". Journal of Toxicology. Clinical Toxicology 31 (3): 407–13. doi:10.3109/15563659309000409. PMID 8355317. 
  31. ↑ Koren G, Graham K, Shear H, Einarson T (December 1989). "Bias against the null hypothesis: the reproductive hazards of cocaine". Lancet 2 (8677): 1440–2. doi:10.1016/S0140-6736(89)92044-8. PMID 2574369. 
  32. ↑ Graham K, Koren G, Klein J, Schneiderman J, Greenwald M (December 1989). "Determination of gestational cocaine exposure by hair analysis". JAMA 262 (23): 3328–30. doi:10.1001/jama.262.23.3328. PMID 2585678. 
  33. ↑ Shamah, David (October 2010). "Hair reveals stress levels and heart attack risks". Israel 21c Innovation News Service.  http://www.israel21c.org/201010218436/health/hair-reveals-stress-levels-and-heart-attack-risks
  34. ↑ Diav-Citrin O, Atanackovic G, Koren G (February 1999). "An investigation into variability in the therapeutic response to deferiprone in patients with thalassemia major". Therapeutic Drug Monitoring 21 (1): 74–81. doi:10.1097/00007691-199902000-00011. PMID 10051057. 
  35. ↑ Olivieri NF, Brittenham GM, McLaren CE, et al. (August 1998). "Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major". The New England Journal of Medicine 339 (7): 417–23. doi:10.1056/NEJM199808133390701. PMID 9700174. 
  36. ↑ Report by the CPSO Discipline Committee, p.3
  37. ↑ Bonetta, Laura (2000). "Hate-mail author trapped by DNA.". Nature Medicine 6 (4): 364. doi:10.1038/74596. PMID 10742127. 
  38. ↑ Birmingham, Karen (2000). "No dismissal for hate-mail author.". Nature Medicine 6 (6): 609–10. doi:10.1038/76146. PMID 10835652. 
  39. ↑ http://islet.org/forum030/messages/27664.htm Alastair Gordon, founder and president of the Islet Foundation, July 26, 2003.
  40. ↑ Olivieri N (July 2002). "I beg to differ". CMAJ 167 (1): 11; author reply 11–2. PMC 116622. PMID 12137065. 
  41. ↑ In the National Post in 1999, Canadian legal columnist, Christie Blatchford called her article on Koren’s involvement in the controversy “They Goaded Him”: Blatchford, Christie. They Goaded Him, National Post, Dec. 26, 1999.
  42. ↑ Naylor CD (February 2002). "The deferiprone controversy: time to move on". CMAJ 166 (4): 452–3. PMC 99355. PMID 11873923. 
  43. ↑ Wanless IR, Sweeney G, Dhillon AP, et al. (September 2002). "Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia". Blood 100 (5): 1566–9. doi:10.1182/blood-2002-01-0306. PMID 12176871. 
  44. ↑ Rund D, Rachmilewitz E (September 2005). "Beta-thalassemia". The New England Journal of Medicine 353 (11): 1135–46. doi:10.1056/NEJMra050436. PMID 16162884. 
  45. ↑ Constantinou G, Melides S, Modell B (February 2003). "The Olivieri case". The New England Journal of Medicine 348 (9): 860–3; author reply 860–3. doi:10.1056/NEJM200302273480919. PMID 12606746. 
  46. ↑ Victorhoffbrand, A (2005). "Deferiprone therapy for transfusional iron overload". Best Practice & Research Clinical Haematology 18 (2): 299–317. doi:10.1016/j.beha.2004.08.026. PMID 15737892. 
  47. ↑ Tanner MA, Galanello R, Dessi C, et al. (April 2007). "A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance". Circulation 115 (14): 1876–84. doi:10.1161/CIRCULATIONAHA.106.648790. PMID 17372174. 
  48. ↑ Miriam Shuchman (2005). The drug trial: Nancy Olivieri and the scandal that rocked the Hospital for Sick Children. Toronto: Random House Canada. ISBN 978-0-679-31084-6. 
  49. ↑ Jerome Kassirer, M.D., former editor of The New England Journal of Medicine and now a professor at Tufts University School of Medicine, University of Buffalo News Center, June 13, 2005 http://www.buffalo.edu/news/7353
  50. ↑ Kollata, Gina. In Drama Pitting Scientist vs. Drug Maker, All Are Punished, New York Times, June 14, 2005. http://www.nytimes.com/2005/06/14/science/14book.html?_r=1
  51. ↑ Gatehouse, Jonathon, Maclean’s Magazine, Toronto, May 4, 2005. http://www.macleans.ca/culture/entertainment/article.jsp?content=20050509_105255_105255
  52. ↑ FDA NEWS RELEASE: FDA Approves Ferripox (deferiprone) to Treat Patients with Excess Iron in the Body, Oct. 14, 2011 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm275814.htm
  53. ↑ http://www.citizen.org/hrg1973
  54. ↑ http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm
  55. ↑ http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM271537.pdf
  56. ↑ http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM271676.pdf
  57. ↑ http://www.cmaj.ca/content/184/2/E155.full http://www.cihr-irsc.gc.ca/e/44772.html
  58. ↑ http://www.motherisk.org/prof/index.jsp http://www.schulich.uwo.ca/moleculartoxicology/ http://www.pharmtox.utoronto.ca/faculty/directory/koren.htm http://www.clinpharmtox.utoronto.ca/aboutus.htm
  59. ↑ http://www.motherisk.org/fas/en/webcast/indexwebcast.html
  60. ↑ Study offers new hope for kids with fetal alcohol syndrome
  61. ↑ Therapeutic Drug Monitoring
  62. ↑ Fetal Alcohol Research
  63. ↑ Canadian Foundation on Fetal Alcohol Research (CFFAR)
  64. ↑ History of Tails at SickKids

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