Research and Advocacy in Nutrition Therapy: Our Specialty Needs YouFrom the Department of Anesthesia, University of Colorado Health Sciences Center, Aurora. Address correspondence to: Paul Wischmeyer, MD, Department of Anesthesia, Leprino Office Building (LOB), 12401 East 17th Ave, B113, Aurora, CO 80045; e-mail: paul.wischmeyer{at}uchsc.edu.
He who refuses to embrace a unique opportunity loses the prize as surely as if he had failed. In my last editorial, I introduced the concept of eliminating the term nutrition support (and nutrition support teams) and replacing it with nutrition therapy (and thus, nutrition therapy teams).1 This month, I will provide concrete examples of how we as a journal, as a society, and as individuals can grow this concept into a new clinical specialty that can take hold as a fundamental part of all patient care. Specifically, to succeed in establishing this new specialty, we must reincarnate our research and advocacy efforts. At the recent European Society of Parenteral and Enteral Nutrition (ESPEN) meeting in Prague, I was struck by the proposal of a global set of nutrition guidelines. In principal, I fully support this notion and applaud the organizers of the prestigious multinational group put together to work toward this goal. However, I believe we are placing the cart squarely before the horse in our specialty. What I would advocate is a multinational, multisociety working group put together to define the key unanswered questions in clinical nutrition therapy (and there are many). This group could then assign the priority with which each question should be answered. There has never been a more important and exciting time to pose such a challenge to the clinical nutrition community. We are amidst a period of incredible growth in funding from the National Institutes of Health and other government agencies for large, multicenter, clinical trials in nutrition. These are needed to give credibility and real answers to the many questions that have remained unanswered in clinical nutrition. The old nutrition support specialty was plagued by a preponderance of small, single-center, and/or underpowered studies. We have attempted to use these often very small trials to create our clinical guidelines. I believe that we as a new nutrition therapy specialty must now approach our clinical trials as cardiology or oncology would approach their new drug trials: with well-designed, appropriately powered, multicenter trials. We are currently close to developing the critical mass to bring to bear a powerful multinational nutrition network of researchers that will be capable of performing these key multicenter trials. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) and the Journal of Parenteral and Enteral Nutrition (JPEN) can and should be catalysts and leaders in this field. Some examples of the key areas that must be acutely addressed include a clearer understanding of the risks and benefits of parenteral nutrition (PN). It is clearly possible that the risks of PN may now be reduced with the advent of glucose control, new lipid emulsions, and an understanding of the risks of overfeeding. New trials examining the safety and efficacy of parenteral nutrients must be undertaken. A major controversy growing in this field is the use of W-6–based lipids in critical illness. Some data suggest that, in the sickest critical care patient, withholding these lipids for an unclear period of time may be beneficial.2 But a more definitive trial is clearly required. Speaking of glucose control, how to safely use glucose control in critically ill patients has now become unclear. Current data leave us quite conflicted with regard to the safety and benefit of tight glucose control in the critically ill patient. The new Glucontrol trial by Dr Preiser and colleagues in Europe has demonstrated a significant mortality risk of hypoglycemia in patients receiving tight glucose control. Of the patients in the tight glucose control arm, 41% had a glucose level <60 mg/dL during their intensive care unit (ICU) stay. These patients had a 2-fold increase in risk of death. This trial also did not show any overall mortality benefit from tight glucose control (J. C. Preiser, personal communication, 2007). This is, of course, in contrast to Dr van den Berghe's findings on the benefits of tight glucose control.3,4 The pending completion of the enormous Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and Canada will help us refine our understanding of the clinical application of this therapy. Clearly, there were a number of differences between the Glucontrol and van den Berghe trials that are beyond the scope of this editorial. However, one difference worth highlighting is that all of the patients in the van den Berghe trials received significant amounts of parenteral calories starting on day 1 of their ICU stay. The Glucontrol trial patients received far less PN and were fed with a standard enteral feeding protocol. As a result, I would submit an alternative hypothesis based on the data as I understand them. Many years ago, Bartlett et al5 published data showing that patients who accumulate a caloric deficit of >10,000 calories during their ICU stay have a mortality rate of 76%. It is possible that the studies of tight glucose control by van den Berghe have actually demonstrated 2 key findings: (1) prevention of a caloric deficit with a mixture of parenteral and enteral nutrition early in ICU care is indeed beneficial if (2) subsequent prevention of the infectious morbidity (and other complications) known to be associated with PN-induced hyperglycemia (via insulin infusion) is provided. This combination of interventions may be what underlies the dramatic mortality benefit van den Berghe observed in her patients. van den Berghe has recently initiated a trial studying the potential benefit of tight glucose control in patients randomized to her method of early PN or a standard enteral feeding protocol. We as a nutrition therapy community must now take up the cause and be willing to bring together a multinational group to define the role of parenteral vs enteral feeding, caloric intake, and preexisting diabetes in the application and safety of glucose control in critical illness. van den Berghe's large single-center trials continue to be the gold standard of clinical research trials in this field; however, as the Glucontrol trial shows us, multicenter trials confirming single-center findings are also mandatory. As a further example, we now live in a new era of nutrition pharmacology in which amino acids and lipids (ie, glutamine, W-3 fats) can be used as pharmacologic interventions to improve outcome (as a drug can) in a variety of clinical settings (please see www.criticalcarenutrition.com for an excellent summary of all of these data). The translational and clinical science behind these new interventions has led to the evolution of the field of nutrition therapy. JPEN and A.S.P.E.N. must continue to be the driving force behind new, large, multinational trials examining these agents. Clinical trials groups created to perform large trials such as the REducing Deaths due to OXidative Stress (REDOXS) trial,6 the GLND trial (information may be found at www.clinicaltrials.gov), and the Scottish Intensive care Glutamine or seleNium Evaluative Trial (SIGNET) in Scotland7 must become the model for a future network of highly qualified clinical nutrition researchers who can answer all of the vital questions facing our specialty. Furthermore, we must not ignore the development of basic translational science in our new specialty. New molecular and genetic techniques are allowing us to begin to understand nutrient mechanisms and pharmacology like never before. I believe a more aggressive push at recruiting basic science research to the nutrition therapy field and to JPEN is vital. Finally, we need to become active and powerful advocates for the Food and Drug Administration (FDA) approval of nutrition therapeutics such as intravenous glutamine dipeptides and more balanced W-3 lipid emulsions in the United States (and Canada). Clinical data over the past 15-20 years reveal that many of these agents may be quite beneficial in improving the outcome in numerous small clinical trials of patients, with virtually no risk to the patient and at a very low cost (see www.criticalcarenutrition.com for examples). A major advantage of nutrition therapeutics is that most have undergone extensive worldwide study and application for, in some cases, many years. Thus, we have extensive safety data and postapproval marketing data, particularly in Europe, where these agents have been used in many thousands of patients. These products are available in virtually every country of the world except the U.S. (and Canada) including many developing nations, such as India and China. It is this author's belief that the FDA must consider creating an alternative approval route for these products, which have a long history of safety and efficacy in Europe and other countries. These postmarket data are powerful and have shown the unequivocal safety of many of these long-used products. Profits from nutrition therapeutics will always be lower than a new synthetic pharmaceutical agent, as patent protection and the profit margin on these naturally occurring agents are limited. Thus, it is difficult for the manufacturers of these nutrition therapeutics to justify the cost of entirely new U.S. safety trials when it is unlikely they will be able recoup these costs. This is key in the global arena of health care economics, as the issues of risk and cost must be paramount to any discussion of any new therapeutic. As an example, the cost of critical care medicine in the U.S. alone was $55 billion per year in 2000, which was 0.56% of the gross domestic product at that time.8 We must as clinical researchers develop therapies that are clinically effective but also fiscally responsible. The issues of clinical efficacy, risk, and cost are exemplified by the story of activated protein C (APC). A drug with significant cost and potential risk to the patient, APC will enter its third major worldwide trial this year in an attempt to refine clinical indications and efficacy. In conclusion, JPEN should aspire to become the leading journal publishing new research in our exciting field of nutrition therapy. Publishing relevant reviews on cutting-edge research techniques is absolutely necessary to help educate nutrition researchers on resources available to improve the impact of their research. Most important, we need to further establish clinical nutrition research as an attractive field for young researchers finishing training (I'll write more on this in future editorials). I see a steady stream of postgraduate/medical students and undergraduate students in my laboratory who are excited about nutrition as a field and research topic. We must keep these students in our field if we wish to have any hope of nutrition therapy growing as a specialty. Ultimately, I see the position of Editor-in-Chief of JPEN as not just an editorial job but also as an advocate, cheerleader, facilitator, and recruiter for the field of nutrition research and nutrition therapy as a whole. Now, what can you do to help our specialty grow? I encourage each of you as readers of JPEN to consider these as your goals for your specialty's future:
As William James stated, we stand at the precipice of a truly unique and exciting opportunity to develop a powerful specialty for improving the outcomes of our patients with efficacious, inexpensive, and safe nutrition interventions. It is up to all of us to embrace this opportunity. Now more then ever, our patients cannot afford for us to fail.
Financial disclosure: none declared.
Journal of Parenteral and Enteral Nutrition, Vol. 32, No. 2,
210-212 (2008) This article has been cited by other articles:
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