Monthly Archives: July 2014

Dr. Damon Scales

PSIF_FTHR_Dr_Damon_ScalesThe Graham Farquharson Knowledge Translation Fellowship: An Incredible Opportunity for Researchers

I feel extremely fortunate to have been the first recipient of the Graham Farquharson Knowledge Translation Fellowship. This award is truly cutting edge and unique for 2 important reasons: First, it is large enough to truly help clinician scientists free themselves from clinical work, so that their time can be devoted to research. Second, it focuses on knowledge translation, targeting research innovations that will truly improve the outcomes of real patients.

Why focus on Knowledge Translation?

Knowledge translation research is the discovery of novel strategies that can be widely disseminated to ensure that patients actually receive the treatments that work. In contrast to the routine quality improvement and continuing medical education activities that occur regularly throughout Canadian hospitals, knowledge translation research employs rigorous study design, standardized measurement of outcome, the generation of scientific knowledge about how to transform medical practice to incorporate best practices, and the skills to engage public policy leaders to sustain these changes.

My Specific Focus: Translating Evidence into Practice for Patients with Anoxic Brain Injury

The specific focus of my fellowship has been on translating evidence into practice for patients with anoxic brain injury. Anoxic brain injury occurs when there is interruption to the flow of blood and hence the delivery of oxygen to the brain. The most common event that leads to diffuse anoxic brain injury is cardiopulmonary arrest, but there are other causes, among them, severe haemorrhage, severe hypotension, traumatic injury, poisonings, and asphyxiation. In all cases, acute severe anoxic brain injury is characterized by diffuse damage to brain tissue and is associated with a high risk of death or disability.

My knowledge translation research has sought to improve how clinicians make predictions about prognosis and treatment recommendations for patients who are in a coma after suffering anoxic brain injury. I have designed and conducted The PremaTOR Trial to test the effectiveness of my knowledge translation approach, which focuses on delivering standardized education, common protocols and pathways, and reminders to help bedside clinicians – nurses and physicians – to make the very best decisions for these vulnerable patients. The ultimate goal is to prevent deaths due to premature termination of life-sustaining treatments yet also to improve the number of patients that survive with good neurological outcomes.

The PremaTOR trial is a stepped-wedge cluster randomized trial (funded jointly by the Canadian Institutes of Health Research and Heart and Stroke Foundation) to evaluate a collaborative network of hospitals that are all using our common strategies to improving the application of evidence-based decision-making for patients who have suffered anoxic brain injury. The trial involved the 18 hospitals that admit the highest annual volume of anoxic brain injury patients in Southern Ontario. Enrolment commenced in November 2011 and concluded in December 2013. We are currently collecting outcome data on all enrolled patients, and anticipate that we will be able to close the study database in June 2014. We will then begin our analyses, and anticipate having a study manuscript ready for peer-reviewed publication before January 2015. This translational research should help increase the proportion of patients that survive with good neurological function, yet also help clinicians more accurately identify patients that are predicted to have no meaningful recovery. The Fellowship funding from Physicians’ Services Incorporated has therefore had 2 direct and very important benefits: it allowed me to have dedicated and protected time to conduct this important knowledge translation research, and it targeted care improvements for more than 800 patients with anoxic brain injury admitted to a large number of Ontario hospitals.

Other Research Catalyzed by The Fellowship

In addition to helping me to complete the PremaTOR Knowledge Translation Trial, The Fellowship has catalyzed my research productivity in several additional ways. It has allowed me to complete and publish more than 25 peer-reviewed manuscripts in the scientific literature during the past 2 years. My notable accomplishments have included a study showing that intravenous magnesium decreases vasospasm yet does not improve clinical neurological outcomes after aneurysmal subarachnoid hemorrhage (J Crit Care 2012); a study demonstrating that routinely obtaining daily chest x-rays for critically ill patients (the usual practice in most ICUs) confers no benefit compared to a more restrictive approach (Crit Care 2012); and a study to identify the most accurate predictors of neurological outcome after anoxic brain injury (Crit Care Med 2014). I also completed and published a population-based cohort study of organ donation patterns in Ontario during the past 17 years. This latter study had important policy implications because it documented wide variation in rates of organ donation after devastating neurological injury across Ontario hospitals, suggesting that strategies are urgently needed to help target low-performing hospitals (CMAJ 2013). The findings of this research were highlighted on the CBC Radio Series White Coat, Black Art in December 2013.

Finally, I have continued to enrol patients into the ICE-PACS trial. This is an individual patient randomized trial to evaluate whether having paramedics start therapeutic hypothermia (i.e. cooling a patient’s body) sooner for patients at high risk of anoxic brain injury after cardiac arrest can lead to better patient outcomes. The underlying premise is that patients should receive treatments that we know are helpful based on when they need them, rather than based on where the patient is located, for example in a hospital versus in an ambulance. The ultimate goal of this translational research study is to increase the number of patients with anoxic brain injury that subsequently survive to hospital discharge with good neurological outcome. The study involves 4 paramedic Emergency Medical Services and 41 destination hospitals in Southern Ontario. This will be one of the largest trials of pre-hospital hypothermia ever conducted and will conclude in December 2015.

Knowledge Translation In Ontario and Beyond

Thanks to the research that the Fellowship has made possible, I have been invited to present my research and ideas at more than 70 local, national, and international meetings, including in the United States, the United Kingdom, and most recently Saudi Arabia. While these presentations have frequently focused on strategies for improving clinical practice, I have more often been asked to speak about the very nature of knowledge translation research, and about how knowledge translation studies should and can be conducted using much more rigorous study designs and evaluations. I believe that this is perhaps the most important unanticipated benefit of my Fellowship funding: it has allowed me to raise awareness of the importance of knowledge translation research, and about the scientific methodologies that can be used to advance our understanding of what works and what doesn’t when seeking to improve clinical practice.

Summary

In summary, the Graham Farquharson Knowledge Translation Fellowship has had a profound impact on my own development as a scientist and knowledge translation researcher, and has helped ensure that my large multicentre and collaborative PremaTOR trial could be successfully completed. More importantly, I believe that this prestigious award from the PSIF has helped raise awareness about the importance of scientific study targeting knowledge translation interventions. This research is absolutely essential for ensuring that our patients actually receive the treatments that are proven to work.

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Dr. Fiona Kouyoumdjian

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Quote:

“The PSIF Resident Research Grant was the first project funding that I ever received, and it allowed me to answer a question from my clinical work with people who were incarcerated. Through that project, I learned about prison health research in Canada, and I developed relationships with people working in this field. I am now building on this foundation to develop a program of research focused on improving the health and health care of people who are incarcerated in Canada.”

In 2008, Dr. Fiona Kouyoumdjian received a Resident Research Grant for $18,000 for her study “The prevalence of gonorrhoea and chlamydia in male inmates in a provincial correctional facility in Ontario.” This project was supervised by Dr. Cheryl Main at McMaster University. Dr. Kouyoumdjian has published three papers in peer-reviewed journals based on this project in the International Journal of STD & AIDS and the Canadian Journal of Public Health. The third is in press (citation: F. G. Kouyoumdjian, L. M. Calzavara, L. Kiefer, C. Main, S.J. Bondy. Drug use prior to incarceration and associated socio-behavioural factors in males in a provincial correctional facility in Ontario, Canada. Canadian Journal of Public Health. In press). Dr. Kouyoumdjian presented her research as a poster presentation at the 2014 PSI Annual General Meeting.

Dr. Kouyoumdjian completed medical school at Dalhousie University, a Master of Public Health at the Johns Hopkins Bloomberg School of Public Health, and residency in Public Health and Preventive Medicine and a PhD in Epidemiology at the Dalla Lana School of Public Health at the University of Toronto. She is currently a Postdoctoral Fellow at the Centre for Research on Inner City Health at St. Michael’s Hospital in Toronto, with Dr. Stephen Hwang as her supervisor, and she works as a Family Physician at a provincial correctional facility. She has a CIHR Fellowship from 2013 to 2016.

Dr. Marc Jeschke

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How did the PSI Funding Help with the Study?

The funding via the PSI Foundation enabled groundbreaking work to provide evidence that glucose can be controlled in severely-burned patients via novel perturbations and that this modulation of glucose is beneficial in terms of outcomes after a burn injury. These results are ultimately leading to an ongoing large prospective clinical trial which hopefully will confirm the benefit of the perturbation.

Description:

PSI Foundation funded Dr. Marc Jeschke of Sunnybrook Health Sciences Centre in Toronto for his study Glucose control in severely burned patients: mechanisms and therapeutic potential. In 2010, PSI approved $165,000 for his 2 year study.

Dr. Jeschke is a Professor in the Department of Surgery and the Department of Immunology at the University of Toronto. He is also the Director of the Ross Tilley Burn Centre and Senior Scientist at the Sunnybrook Research Institute.

Dr. Jeschke has had several papers resulting from this research, including publications in Lancet and the Annals of Surgery.

Publications

  1. Abdullahi A, Amini-Nik S, Jeschke MG. Animal models in burn research. Cell Mol Life Sci. 2014 Apr. 2014 Apr 9. [Epub ahead of print].
  2. Stanojcic M, Chen P, Harrison RA, Wang V, Antonyshyn J, Zúñiga-Pflücker JC, Jeschke MG. Leukocyte Infiltration and Activation of the NLRP3 Inflammasome in White Adipose Tissue Following Thermal Injury. Crit Care Med. 2014 Mar. 2014 Feb 26. [Epub ahead of print].
  3. Diao L, Marshall AH, Dai X, Bogdanovic E, Abdullahi A, Amini-Nik S, Jeschke MG. Burn Plus Lipopolysaccharide Augments Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation and Reduces PGC-1α in Liver. Shock. 2014 Feb. Feb;41(2):138-44. doi: 10.1097/SHK.0000000000000075.
  4. Jeschke MG, Pinto R, Herndon DN, Finnerty CC, Kraft R. Hypoglycemia Is Associated With Increased Postburn Morbidity and Mortality in Pediatric Patients. Critical Care Medicine. 2013 Dec. 2013 Dec 23. [Epub ahead of print].
  5. Jeschke MG, Herndon DN. Burns in children: standard and new treatments. Lancet. 2013 Sep. Lancet. 2013 Sep 10. doi:pii: S0140-6736(13)61093-4. 10.1016/S0140-6736(13)61093-4. [Epub ahead of print].
  6. Jeschke MG. Clinical review: Glucose control in severely burned patients – current best practice. Crit Care. 2013 Jul. 2013 Jul 25;17(4):232. [Epub ahead of print].
  7. Jeschke MG, Finnerty CC, Kulp GA, Kraft R, Herndon DN. Can we use C-reactive protein levels to predict severe infection or sepsis in severely burned patients? Int J Burns Trauma. 2013 Jul. 2013 Jul 8;3(3):137-43. Print 2013.
  8. Kraft R, Herndon DN, Mlcak RP, Finnerty CC, Cox RA, Williams FN, Jeschke MG. Bacterial respiratory tract infections are promoted by systemic hyperglycemia after severe burn injury in pediatric patients. Burns. 2013 Sep. 2013 Sep 25. doi:pii: S0305-4179(13)00229-5. 10.1016/j.burns.2013.07.007. [Epub ahead of print].
  9. Hiyama Y, Marshall AH, Kraft R, Arno A, Jeschke MG. Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress. J Surg Res. 2013 Jul. 2013 Jul 4. doi:pii: S0022-4804(13)00659-8. 10.1016/j.jss.2013.06.029. [Epub ahead of print].
  10. Jeschke MG, Gauglitz GG, Finnerty CC, Kraft R, Mlcak RP, Herndon DN. Survivors Versus Nonsurvivors Postburn: Differences in Inflammatory and Hypermetabolic Trajectories. Ann Surg. 2013 Apr. 2013 Apr 10. [Epub ahead of print].
  11. Brooks NC, Marshall AH, Qa’aty N, Hiyama Y, Boehning D, Jeschke MG. XBP-1s is Linked to Suppressed Gluconeogenesis in the Ebb Phase of Burn Injury. Mol Med. 2013 Mar 15. doi: 10.2119/molmed.2012.00348. [Epub ahead of print].
  12. Kraft R, Herndon DN, Finnerty CC, Shahrokhi S, Jeschke MG. Occurrence of Multiorgan Dysfunction in Pediatric Burn Patients: Incidence and Clinical Outcome. Annals of Surgery. 2013 Mar 18. [Epub ahead of print].
  13. Marshall AH, Brooks NC, Hiyama Y, Qa’aty N, Al-Mousawi A, Finnerty CC, Jeschke MG. Hepatic Apoptosis Postburn Is Mediated by C-Jun N-Terminal Kinase 2. Shock. 2013 Feb;39(2):183-8.
  14. Hiyama Y, Marshall AH, Kraft R, Qa’aty N, Arno A, Herndon DN, Jeschke MG. The Effects of Metformin on Burn Induced Hepatic Endoplasmic Reticulum Stress in Male Rats. Mol Med. 2013 Mar 5;19:1-6.
  15. Kraft R, Herndon DN, Finnerty CC, Hiyama Y, Jeschke MG. Association of Postburn Fatty Acids and Triglycerides with Clinical Outcome in Severely Burned Children. J Clin Endocrinol Metab. 2013 Jan;98(1):314-21. doi: 10.1210/jc.2012-2599. Epub 2012 Nov 12.
  16. Kulp GA, Tilton RG, Herndon DN, Jeschke MG. Hyperglycemia exacerbates burn-induced liver inflammation via noncanoncial NF-κB pathway activation. Molecular Medicine. 2012 Sep 7;18:948-56.
  17. Jeschke MG*, Williams FN*, Finnerty CC, Rodriguez N, Kulp GA, Ferrando AA, Norbury WB, Suman OE, Kraft R, Branski LK, Al-mousawi A, Herndon DN. The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes. PLoS One. 2012;7(5):e35465. Epub 2012 May 11.
  18. Song J, Finnerty CC, Herndon DN, Kraft R, Boehning D, Brooks NC, Jeschke MG. Thermal injury activates the eEF2K-dependent eEF2 pathway in pediatric patients. JPEN. 2012 Sep;36(5):596-602.