特邀述评：临床营养支持疗法需要精打细算
Clin Nutr. 2016 Feb;35(1):5-6.
Numbers which count.
Laviano A.
Department of Clinical Medicine, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.
Malnutrition and reduced food intake are strong predictors of negative outcome in hospitalized patients [1]. In contrast, whether nutrition support is an effective therapy to treat disease-related malnutrition and improve clinical outcome of malnourished hospitalized patients remains to be robustly demonstrated by large, prospective, randomized clinical trials. Although seemingly obvious, reducing weight loss or restoring body weight gain by nutrition support, i.e., counseling, oral nutritional supplements (ONS), enteral nutrition or parenteral nutrition, is not necessarily associated with improved clinical outcome, i.e., morbidity, quality of life, mortality [2]. This sort of misunderstanding might have contributed to the insufficient implementation of nutritional care in hospitals across the planet [3]. Indeed, clinicians may value the role of nutritional status in preserving healthy conditions, but they may also prioritize other outcome measures in hospitalized patients rather than only body weight. Therefore, it appears that clinical trials targeting clinical rather than only nutritional outcome measures could have amajor impact on changing daily practice [4].
Recently published data might have contributed to the skepticism toward nutrition therapy as an effective and efficient strategy to improve clinical outcome, beyond restoring nutritional status of malnourished hospitalized patients. In their systematic review and meta-analysis, Bally et al. showed that nutritional support in medical inpatients increases body weight, caloric and protein intake, but has no impact on mortality, hospital-acquired infections, functional outcome or length of stay [2]. However, nutritional support decreases non-elective readmissions [2]. More recently, Vlooswijk et al. showed in oropharyngeal cancer patients treated with radiotherapy that dietary counseling and nutrition support do not stop weight loss [5]. Although very much interesting, both papers present significant limitations: the overall quality of the studies included in the meta-analysis is low and their heterogeneity is high [2], whereas the Vlooswijk et al.'s paper is retrospective and cannot precisely define the timing of counseling/nutrition support initiation [5]. Nevertheless, these data highlight the need of good quality, adequately powered and clinically oriented trials.
Addressing this need, Deutz et al. studied more than 600 older, malnourished hospitalized patients who were randomly allocated to receive during hospitalization and after discharge either a specialized, energy-dense ONS or a carbohydrate-only ONS [6]. The primary goal was composite 90-day post-discharge incidence of death or non-elective readmission. The results obtained showed that supplementation with an energy-dense, specialized ONS extending beyond discharge improved body weight but could not reduce readmission rate. However, it significantly reduced postdischarge mortality. It is acknowledged that the paper has limitations, as also correctly pointed out by the authors, which include limited generalizability and possible selection bias. Nevertheless, a number of key features of the paper are worth of mentioning to provide a general template for future studies.
Quantitatively and qualitatively appropriate protein intake appears to represent a key factor in improving outcome. In this light, it is interesting to note how Deutz et al.'s results are consistent with data from a large epidemiological observation, which show that larger protein intake in older adults >65 yrs is associated with reduced mortality [7]. However, this goal can be achieved only if quantitatively and qualitatively appropriate protein intake is consumed long enough to induce and maintain positive anabolic responses. In this light, Deutz et al.'s paper demonstrated that limiting ONS to the hospitalization period may not be sufficient to trigger positive anabolic responses, particularly if one considers that the average length of stay in most hospitals across the planet is less than 10 days.
Finally, their calculation of the number needed to treat (NNT) is of great interest and relevance. Deutz et al. showed that 20 patients should be treated to save 1 death [6]. Their decision to provide this information is interesting since it associates nutritional support to pharmacological therapies, and it is relevant since the NNT for this specific ONS is quite encouraging. Indeed, Schork has recently reviewed the NNT for some blockbuster drugs, and it is surprising to note that the NNT for esomeprazole is 24 [8].
Comparing these new data with those from the past, it seems that a new era for clinical nutrition is emerging. Nutritional support is slowly changing from a "one-size-fits-all" support to precision medicine, in which the metabolic complexity of the underlying disease, the age of the patients, the timing and duration of intervention, as well as the quality and the quantity of the macro- and micronutrients will concur to devise the more appropriate nutritional therapy.
References
Hiesmayr M, Schindler K, Pernicka E, Schuh C, Schoeniger-Hekele A, Bauer P, et al. Decreased food intake is a risk factor for mortality in hospitalised patients: the nutrition day survey 2006. Clin Nutr. 2009;28:484-91.
Bally MR, Blaser Yildrim PZ, Bounoure L, Gloy VL, Mueller B, Briel M, et al. Nutritional support and outcomes in malnourished medial in patients. A systematic review and meta-analysis. JAMA Intern Med. 2016;176:43-53.
Schindler K, Pernicka E, Laviano A, Howard P, Schutz T, Bauer P, et al. How nutritional risk is assessed and managed in European hospitals: a survey of 21,007 patients. Findings from the 2007e2008 cross-sectional nutrition day survey. Clin Nutr. 2010;29:552-9.
Laviano A, Fearon KCH. The oncology wall: could Ali Baba have got to the nutrition treasure without using the correct words? Clin Nutr. 2013;32:6-7.
Vlooswijk CP, van Rooij PHE, Kruize JC, Schuring HA, Al-Mamgani A, de Roos NM. Dietary counselling and nutritional support in oropharyngeal cancer patients treated with radiotherapy: persistent weight loss during 1-year follow-ups. Eur J Clin Nutr. 2016;70:54-9.
Deutz NE, Matheson EM, Matarese LE, Baggs GE, Nelson JL, Hegazi RA, et al. Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial. Clin Nutr. 2016;35:18-26.
Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19:407-17.
Schork NJ. Time for one-person trial. Nature. 2015;520:609-11.
PMID: 26857913
DOI: 10.1016/j.clnu.2016.01.011