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Clinical Study
Reference
Lower GI
Braga 2002 (Surg)............................. 17
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IMPACT® Clinical Study Reference
Introduction
Nestlé HealthCare Nutrition, Inc. leads the way in innovative products backed by
high levels of clinical research. This booklet provides health care professionals
with study summaries of the key clinical trials and meta-analyses providing
evidence for the role of IMPACT® formulas in supporting improved patient outcomes.
Mechanisms of Action
The IMPACT® family of enteral formulas contains a unique blend of three
synergistic immunonutrients:
Arginine:
• Supports host immune response by promoting T-lymphocyte
growth and replication, and nitrogen retention.4-7
• Increases levels of hydroxyproline, the main precursor for
collagen, thereby playing a role during wound management.4-7
• Increases gut oxygenation and colonic microperfusion.8
• Stimulates synthesis of nucleotides in vitro.9
Dietary Nucleotides:
• Support replication of the rapidly dividing cells of the immune system, i.e.,
T-lymphocytes, by providing a source of purine and pyrimidine bases for
DNA/RNA production.10
Omega-3 Fatty Acids:
• Modulate cytokines to produce less inflammatory and less
immunosuppressive mediators.11.12
• Produce less inflammatory prostaglandins (PGE3) to help to
alleviate arginine deficiency by reducing induction of arginase I.13
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IMPACT® Clinical Study Reference
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Health Economic Outcomes
$1,000 $961
$500 $391
$0
0% 5% 10% 15% 20% 25% 30% 35%
Base Complication Rate
These calculations are designed to help illustrate the potential cost savings to a facility with the use
of a specific immunonutrition formula. They are not intended to guarantee any specific reductions in
cost, infectious or other complication rates.
*The improvement in outcome shown by these calculations is based on the observed decrease in infectious
complications analyzed for perioperative use of IMPACT® Nutritional Therapy by Waitzberg et al. The
potential estimated cost savings shown by these calculations is based on hospital cost data from the HCUP
database computed in 2010 dollars. Formula cost is per published distributor prices.
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IMPACT® Clinical Study Reference
*IMPACT® Nutritional Therapy has been associated with reduced cost of hospital care despite its higher purchase
price vs. standard formulas. Assumes patients received 14 days of isocaloric/isonitrogenous feedings of
IMPACT® 1.5 formula or Promote®. Formula cost in these financial calculations is based on the cost of formula
referenced in the study. Actual pricing will vary.
**Assumes cost of incremental care is $2400/day.
†These financial calculations are based on certain estimates and assumptions, are for illustrative purposes only
and are not a prediction or guarantee of savings at any specific institution.
Promote® is a registered trademark of Abbott Laboratories.
◊
8
Marano L, Profidia R, Pezzella M, Mauskopf JA, Candrilli SD,
Grassia M, Petrillo M et al. Chevrou-Séverac H, Ochoa JB.
Ann Surg Oncol 2013; July 10 2013 DOI: Immunonutrition for patients
10.1245/s1043401330881. undergoing elective surgery for
Randomized controlled trial done to gastrointestinal cancer: Impact on
investigate the effect of early post-op hospital costs. WJSO 2012:10:136;
immunonutrition on outcomes in gastric doi:10.1186 1477-7819-10-136.
cancer patients undergoing gastrectomy
(n=109). Post-operative feedings were This study was completed to create a health
administered 6 hours post-op via jejunal economic model to determine the impact on
tube and continued until post-op day 7. hospital costs of immunonutrition (IMPACT®
Formulas were isonitrogenous and formulas) used in patients having major
isocaloric, however the study group tube elective surgery for gastrointestinal (GI)
feeding contained supplemental L-arginine, cancer). United States (US) hospital costs
n-3 fatty acids and nucleotides and the were taken from the Healthcare Cost and
control group received standard formula. Utilization Project’s Nationwide Inpatient
Infectious complications in the study group Sample (HCUP-NIP) database. These
were significantly lower than in the control costs were used to estimate the effect of
group (7.4% vs. 20%, p<0.05), as was the immunonutrition on hospital costs using
rate of anastomotic leak (3.7% vs 7.3%, reductions in length of stay (LOS) and risk
p<0.05). LOS for the intervention group was of complications from a meta-analysis of 14
3.2 days less than for the control group RCTs studying use of IMPACT® formulas in
(p=0.029). GI cancer surgery patients (n=889).
Meta-analysis estimates show perioperative
use of IMPACT® resulted in savings per
patient of $6000 when costs were based
on reduction in LOS, and a $3300 savings
when costs were based on a reduction in
infectious complications. The sensitivity
analysis showed cost savings were present
for baseline complication rates above
3.5%. When US baseline rates for LOS and
infectious complications for upper and
lower GI cancer surgery were inserted
in the model, cost savings continued to
present (range, $1200 to $6300).
Use of immunonutrition for patients
undergoing elective surgery for GI cancer
was concluded an effective and cost-saving
intervention.
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IMPACT® Clinical Study Reference
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Marik P, Zaloga G. Felekis D, Eleftheriadou A, Papadakos
Immunonutrition in high-risk G, Bosinakou I, Ferekidou E, Kandiloros
surgical patients: A systematic D, Katsaragakis S et al.
review and analysis of the Effect of Perioperative Immuno-
literature. JPEN. 2010; 34(4): Enhanced Enteral Nutrition on
378-386. Inflammatory Response, Nutritional
Status, and Outcomes in Head and
This meta-analysis reviewed 21 prospective Neck Cancer Patients Undergoing
controlled trials (n=1,918) to evaluate the
Major Surgery. Nutr and Cancer
effect of immune-modulating nutrition
vs. control formula on clinical outcomes 2010; 62(8): 1105-1112.
of high-risk elective surgery patients.
A randomized, double-blinded, prospective
Sixteen of 21 studies utilized IMPACT®
study done to evaluate that immunonutrition
formula pre-, peri- or post-surgically
supplemented with arginine, RNA and n-3
with GI, Head & Neck or Cardiac surgery
fatty acids improves outcomes in head
patients. Studies were stratified by formula
and neck cancer patients with squamous
type and timing of initiation. Although
cell carcinoma undergoing surgery.
no difference was noted in mortality
Formulas were isocaloric and the study
across groups, intention-to-treat analyses
group received ORAL IMPACT® 5 days
showed immunonutrition associated with
prior to surgery and IMPACT® tube feeding
a 38%-61% reduction in hospital acquired
post-surgery. The control group received
infections (p<0.0001), a 9%-60% reduction
no supplemental nutrition before surgery
in wound complications (p=0.02), and on
and standard tube feeding post-surgery.
average, a 3 day reduction in hospital LOS
Major complications included pneumonia,
(p<0.001). Benefits were found to be similar
UTI, fistula and wound infection, and were
for peri- and postoperative use; however,
followed until discharge (median = 12
formulas containing both arginine and fish
days). Rate of major complications was
oil (as opposed to a single immunonutrient)
significantly lower in the immunonutrition
were required, presumably due to
vs. the standard group (5% vs. 25%; p<0.05).
synergistic effect. As the majority of studies
Perioperative IMPACT® in head and neck
utilized a product containing arginine,
cancer surgery patients may influence post-
fish oil, nucleotides and antioxidants, it is
operative outcomes by reducing infections
unclear if benefits can be extrapolated to
and wound complications.
immune-modulating formulas of differing
composition. Although optimal timing is
a matter for further research, authors
suggest beginning immunonutrition 5 days
preoperatively and continuing into the
postoperative period, when feasible.
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IMPACT® Clinical Study Reference
12
Tepaske R, Velthuis HT, Oudemans-Van Waitzberg DL, Saito H, Plank LD,
Straaten HM, Bossuyt PMM, Schultz JM, Jamieson GG, Jagannath P,
Eijsman L, Vroom M. Tsann-Long H, Mijares JM, Bihari D.
Glycine does not add to the Postsurgical infections are reduced
beneficial effects of perioperative with specialized nutrition support.
oral immune-enhancing nutrition World J Surg. 2006; 30:1592-1604.
supplements in high-risk cardiac
surgery patients. JPEN. 2007; 31(3): This article reviewed 17 studies (n=2,305)
173-180. where IMPACT® formula was used before
and/or after major elective surgery and
A prospective, randomized study to the clinical outcomes reported were
measure outcomes of the addition of included in this meta-analysis. Ten studies
glycine to an oral immune-enhancing compared preoperative or perioperative
nutrition supplement (ORAL IMPACT®+ IMPACT® formula provision vs. control and
glycine) as compared to a standard oral 7 studies looked at postoperative nutrition.
immune-enhancing nutrition supplement Fourteen studies examined IMPACT®
(ORAL IMPACT®) and a control group formula used with gastrointestinal (GI)
receiving standard nutrition. Each cancer surgeries. IMPACT® formula
nutrition supplement was administered supplementation was associated with
for a minimum of 5 preoperative days. significant reductions in postoperative
Patients (n=70) were 70 years of age or infectious complications (39-61%) and
older and were planned for mitral valve a significant decrease in hospital stay
surgery. Outcomes of morbidity, organ by an average of 2 days. Anastomotic
function and postoperative recovery leaks were found to be less prevalent
were analyzed. In both groups receiving in gastrointestinal surgery patients who
the ORAL IMPACT® formula, infectious received IMPACT® formula perioperatively.
morbidity was decreased (17%/23% vs. Overall, 500 mL-1 L of IMPACT® formula
50%) as compared to the control (p=0.02). 5-7 days preoperatively contributed to
Conclusions of the study were that use improved outcomes in GI, cardiac, and
of preoperative ORAL IMPACT® formula head/neck elective surgery patients.
reduces the rate of infectious morbidity
Cited by:
and results in more hemodynamic stability.
The addition of glycine did not result in any CRITICAL CARE NUTRITION
additional benefit. GUIDELINES1
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IMPACT® Clinical Study Reference
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Braga M, Gianotti L, Vignali A, Strickland A, Brogan A, Krauss J,
Schmid A, Nespoli L, Di Carlo V. Martindale R, Cresci G.
Hospital resources consumed Is the use of specialized nutritional
for surgical morbidity: effects of formulations a cost-effective
preoperative arginine and n-3 fatty strategy? A national database
acid supplementation on costs. evaluation. JPEN. 2005; 29
Nutrition. 2005; 21: 1078-1086. (1 Suppl): S81-91.
This article uses results from a This article uses a current review on
prospective, randomized, placebo- the literature of published outcomes
controlled study22 of preoperative of studies using clinical outcomes with
immunonutrition supplementation immune-modulating diets to determine
(IMPACT® formula) to calculate hospital the potential economic benefit associated
costs for post-operative complications, with the use of specialized nutritional
and analyze for the possibility of formulations in elective surgical trauma
cost savings in upper and lower GI and medical patients. Data was obtained
cancer patients. A blinded cost-analysis from a large national database of 126
for hospital length of stay (LOS) and member hospitals and over 1 million
in-patient resource utilization for patients. Data was collected on patient
infectious and non-infectious type, subservice, complication, mean
complications were referenced to the length of stay, mean cost and incremental
National List of Sanitary Costs, Italian cost per complication (if experienced). For
Ministry of Health. Mean cost the medical patient population, specialized
of treating infectious complications nutritional formulations found a 51%
was significantly lower in the IMPACT® decrease in infectious complications
formula vs. conventional group and decreased length of stay of 9.7
(p=0.05). Because patients receiving days resulting in a net cost savings of
preoperative IMPACT® formula had $2,066 per patient. Net cost savings for
significantly fewer infectious surgical and trauma patients was $688
complications and significantly shorter and $308 per patient respectively. This
LOS, total cost per patient was €5668 data demonstrated that specialized
vs. €7092 for conventional treatment. formulations are a cost-effective way to
Preoperative immunonutrition with improve clinical outcomes while reducing
IMPACT® formula resulted in a net resource consumption.
hospital savings per patient of €1424, Cited by:
as compared to conventional care.
GUIDELINES ON ENTERAL
Cited by:
NUTRITION: SURGERY 2
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
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IMPACT® Clinical Study Reference
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Braga M, Gianotti L, Nespoli L, Braga M, Gianotti L, Vignali A,
Radaelli G, Di Carlo V. Di Carlo V.
Nutritional approach in Preoperative oral arginine and n-3
malnourished surgical patients. fatty acid supplementation improves
Arch Surg. 2002; 137: 174-180. the immunometabolic host response
and outcome after colorectal
Prospective, randomized, controlled trial resection for cancer. Surgery. 2002;
of 150 patients requiring major elective 132: 805-814.
surgery of the GI tract for malignancy. All
enrolled patients were malnourished with A prospective, randomized, controlled trial
≤10% body mass loss and randomized of 200 patients with colorectal neoplasm
to 3 groups. Group 1 (Perioperative requiring surgical resection. The 4 groups
Treatment Group) was supplemented were randomized to: Group 1, perioperative
preoperatively with 1 liter per day ORAL supplementation with ORAL IMPACT®
IMPACT® formula for 7 consecutive days formula for 5 days preoperatively +
and tube fed with IMPACT® formula post- ORAL IMPACT® or IMPACT® tube feeding
operatively. Group 2 (Preoperative Group) postoperatively; Group 2, preoperative
was supplemented with 1 liter per day of ORAL IMPACT® for 5 days; Group 3 (control),
ORAL IMPACT® formula for 7 consecutive iosnitrogenous/caloric oral supplement
days preoperatively and standard formula preoperatively for 5 days; and Group 4; no
post-op. Group 3 (Control Group) received supplementation before or after surgery
standard tube feeding post-operatively. All (conventional therapy). Immune response
diets were isocaloric and isonitrogenous. (p<0.05), gut oxygenation (p<0.01) and
Results reveal that the perioperative microperfusion (p<0.02) were found to
treatment group experienced decreased be significantly better for Groups 1 and
complications (p=0.02), and both treatment 2. Overall, Groups 1 and 2 fed IMPACT®
groups had a reduced length of hospital formula both perioperatively and
stay as compared to the control group preoperatively had outcomes of decreased
(p=0.01, p=0.001). infectious complications (p<0.02 p<0.04);
Cited by: reductions in antibiotic therapy days
(p<0.005, p<0.004) and length of hospital
GUIDELINES ON NUTRITIONAL stay (p<0.0005) as compared to the control
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3 and conventional therapy groups.
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2 GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
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IMPACT® Clinical Study Reference
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
18
Snyderman CH, Kachman K, Braga M, Gianotti L, Vignali A,
Molseed L, et al. Radaelli G, Mari G, Di Carlo V.
Reduced postoperative infections Perioperative immunonutrition
with an immune-enhancing in patients undergoing cancer
nutritional supplement. surgery. Results of a randomized
Laryngoscope. 1999; 109: 915-921. double-blind phase 3 trial. Archives
of Surgery. 1999; 134: 428-433.
A prospective, randomized, double-blind,
study of 136 head and neck cancer One hundred and seventy-one patients
patients who received IMPACT® formulas who required major surgery for gastric,
pre- and postoperatively or postoperatively pancreatic or colorectal cancer were
alone versus a standard formula pre- and randomized in a double-blind fashion to
post-operatively or postoperatively alone. receive either a formula supplemented
IMPACT® formula-fed patients (pre- and with arginine, omega-3 fatty acids and
postoperatively and post-operatively dietary nucleotides (IMPACT® formula,
only) had nearly half as many infections n=102), or an isocaloric, isonitrogenous
compared to patients in the standard control (n=104). For seven days prior to
formula groups (p=0.02 p=0.04). There was surgery, patients consumed 1 liter/day
no difference in length of stay; however, of either the control or the supplemented
there was a trend toward shorter length formula. After surgery, patients received
of ICU stay and potential cost savings for the same preoperative formulas via jejunal
patients fed IMPACT® formula. feeding and continued on the formula for
Cited by: 7 days. Patients who received the IMPACT®
formula perioperatively had significant
GUIDELINES ON ENTERAL reduction in postoperative infection (9/85
NUTRITION: SURGERY 2 in the supplemented group compared to
21/86 in the control group, p=0.02). There
was also significant reduction in length of
hospitalization for the group that received
IMPACT® formula (p=0.01).
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
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IMPACT® Clinical Study Reference
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
20
Braga M, Gianotti, Vignali A, Senkal M, Mumme A, Eickhoff U,
Cestari A, Bisagni P, Di Carlo V. Geier B, Spath G, Wulfert D,
Artificial nutrition after major Joosten U, Frei A, Kemen M.
abdominal surgery: IMPACT of Early postoperative
route of administration and immunonutrition: clinical outcome
composition of the diet. Crit Care and cost-benefit analysis in surgical
Med. 1998; 26(1): 24-30. patients. Crit Care Med. 1997; 25(9):
1489-1496.
A prospective, randomized trial of 166
patients undergoing surgery for gastric A prospective, randomized, multi-center
or pancreatic cancer randomized to study of 164 patients with upper GI
receive IMPACT® formula, standard enteral cancer who underwent major surgery and
formula or total parenteral nutrition (TPN). received early postoperative feeding with
The nutritional regimens were isocaloric IMPACT® formula or an isonitrogenous,
and isonitrogenous. Patients receiving isocaloric control formula without
IMPACT® formula had the fewest number supplemental arginine, dietary nucleotides
of postoperative infections (p<0.05) and or fish oil. Patients who received IMPACT®
a shorter hospital stay compared to the formula had 53% fewer infectious and
standard formula or TPN. In sub-groups wound complications occurring after day
of malnourished patients and patients five postoperatively (p<0.05). The average
who received homologous transfusions, cost for treating complications was 32%
administration of IMPACT® formula lower for the IMPACT® formula group.
compared more favorably than TPN at
Cited by:
reducing severity of infection and length
of hospital stay (p<0.05). This study GUIDELINES ON ENTERAL
included data from a 1995 study published NUTRITION: SURGERY 2
in Infusionsther Transfusionmed with an
additional 89 patients.
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
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IMPACT® Clinical Study Reference
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
22
Tepaske R, Thio S, Eysman l, Daly JM, Weintraub FN, Shou J,
van Deventer L, Ince C, et al. Rosato EF, Lucia M.
Perioperative immunonutrition Enteral nutrition during
in “high risk” cardiac surgery multimodality therapy in upper
patients improves immunological gastrointestinal cancer patients.
parameters and clinical outcome. Ann Surg. 1995; 221(4): 327-338.
Presented at the european society
of surgical infection meeting, Oslo, A prospective, randomized, double-blind
June 1997. study of 60 patients with upper GI cancer
who underwent abdominal surgery and
A prospective, randomized, placebo received early postoperative feeding with
controlled double-blind study of 50 either IMPACT® formula or TraumaCal®
patients undergoing heart surgery. formula*. Patients fed IMPACT® formula
Patients consumed ORAL IMPACT® had 77% fewer infectious and wound
formula or an isocaloric control complications (p<0.005) and had a six day
formula for 5 – 10 days before shorter mean length of hospitalization
surgery. Patients who received ORAL than patients in the TraumaCal® group
IMPACT® formula had significantly (p=0.02).
fewer lower respiratory tract infections Cited by:
(0 of 22 vs. 5 of 23, p=0.022) and 65%
reduction in total infections compared GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
to the group that received the ANTI-CANCER TREATMENT3
control formula (p=0.009).
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Abbott Laboratories.
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IMPACT® Clinical Study Reference
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
24
References to nutritional guidelines in this document do not constitute endorsements by or on
behalf of any organization.
References:
1. McClave SA et al. Guidelines for the provision and assessment of nutrition support therapy in the
adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral
and Enteral Nutrition. JPEN. 2009; 33(3): 277-316.
2. Weimann A et al. ESPEN guidelines on enteral nutrition: surgery including organ
transplantation. Clin Nutr. 2006; 25: 224-244.
3. August DA et al. A.S.P.E.N. Clinical Guidelines: nutrition support therapy during adult
anticancer treatment and in hematopoietic cell transplantation. JPEN. 2009; 33(5): 472-500.
4. Ochoa JB et al. A rational use of immune enhancing diets: when should we use dietary arginine
supplementation? NCP 2004; 19 (3): 216-225.
5. Zhu X et al. Immunosuppression and infection after major surgery: a nutritional deficiency. Crit
Care Clin 2010; 26(3): 491-500.
6. Wu G et al. Arginine metabolism and nutrition in growth, health and disease. Amino Acids 2009;
3(0) 153-168.
7. de Aguilar- Nascimento JE et al. Role of enteral nutrition and pharmaconutrition in conditions
of splanchnic hypoperfusion. Nutrition 2010; 26(4): 354-358.
8. Barbul A. Arginine biochemistry, physiology and therapeutic implications. JPEN.
1986; 10: 227-238.
9. Yamauchi K et al. Glutamine and arginine affect Caco-2 proliferation by promotion of nucleotide
synthesis. Nutrition. 2002; 18: 329-333.
10. Grimble GK et al. Nucleotides as immunomodulators in clinical nutrition. Curr Opin in Clin Nutr
and Metab Care. 2001; 4(1): 57-64.
11. Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins, Leukotrienes and
Essential Fatty Acids. 2006; 75: 197-202.
12. Mizock BA. Nutritional support in acute lung injury and acute respiratory distress syndrome.
NCP. 2001; 16: 319-328.
13. Bansal V et al. Interactions between fatty acids and arginine metabolism: implications for the
design of immune enhancing diets. JPEN. 2005; 29(1): S75-S80.
14. Drover JW et al. Perioperative use of arginine-supplemented diets: a systematic review of the
evidence. J Am Coll Surg; 2011; 212 (3): 385-399.
15. Waitzberg DL et al. Postsurgical infections are reduced with specialized nutrition support.
World J Surg. 2006; 30: 1592-1604.
16. Braga M et al. Preoperative oral arginine and n-3 fatty acid supplementation improves the
immunometabolic host response and outcomes after colorectal resection for cancer. Surg.
2002; 132(5): 805-814.
17. Atkinson S et al. A prospective, randomized, double-blind, controlled clinical trial of enteral
immunonutrition in the critically ill. Crit Care Med. 1998; 25: 1164-1172.
18. Bower RH et al. Early enteral administration of a formula (IMPACT formula) supplemented
with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter,
prospective, randomized, clinical trial. Crit Care Med. 1995; 23(3): 436-449.
19. HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization (HCUP). 2008. Agency
for Healthcare Research and Quality, Rockville, MD. www.hcup-us.ahrq.gov/nisoverview.jsp.
20. Farber MS et al. Reducing costs and patient morbidity in the enterally fed intensive care unit
patient. JPEN. 2005; 29(1 Suppl): S62-S69.
21. Jencks SF et al. Rehospitalization among patients in the Medicare free-for-service program.
NEJM 2009; 360: 1418-1428.
22. Gianotti L et al. Randomized controlled trial of preoperative oral supplementation with a
specialized diet in patients with gastrointestinal cancer. Gastroenterol 2002; 122: 1763-1770.
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