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Enteral Nutrition and Oral Nutrition Supplements: A Review of the Economics Literature

Posted on: Sunday, 15 January 2006, 03:02 CST

By Pritchard, Clive; Duffy, Steven; Edington, Jackie; Pang, Francis

ABSTRACT. Background: We sought to review the economics literature on enteral nutrition (EN) and oral nutrition supplements (ONS) against the background of an ongoing clinical guideline development. Methods: We searched the Health Economic Evaluations Database, the NHS Economic Evaluation Database, and the Cochrane Database of Systematic Reviews. Results: Enteral vs parenteral nutrition was found to be the most common comparison undertaken. The randomized trial evidence suggests that, in some groups of patients, EN is better in terms of clinical endpoints and/or length of hospital stay. This should translate into a lower mean cost for EN, given the reduced daily cost. These studies should be treated with caution because of their small sample size and poor quality. Costing was often crude and poorly reported, tending to focus on the narrow costs of the nutrition supplements. Only 1 study of a nutrition supplement in the community setting was found. Conclusions: There is some evidence to indicate economic advantages of enteral over parenteral nutrition and of immune-enhancing supplements relative to control diet. There is a lack of well-designed studies taking a broad view of relevant comparators, costs, and outcomes. The cost- effectiveness of different forms of nutrition in different patient groups remains to be established. (Journal of Parenteral and Enteral Nutrition 30:52-59, 2006)

Economic considerations are becoming more widespread as a component of decision-making processes with regard to medicines and other health care technologies. In the UK, economic analysis has formed an important element of the technology appraisals conducted by the National Institute for Clinical Excellence (NICE) and is expected to form part of the evidence base in its growing clinical guidelines program. One of the key principles of NICE's clinical guidelines is that they "address the cost-effectiveness of treatments or management approaches."1

NICE's work program includes a clinical guideline on nutrition support in adults. The scope of the guideline2 expresses NICE's concern with economic aspects of patient management by reporting a 1992 estimate of 260 million per year that could be saved by the NHS with improvements in the recognition and treatment of patients with malnutrition. Therefore, there is a need for a summary of the relevant economic evidence in artificial nutrition. The aim of this paper is to summarize the findings of a review of the economic evidence on the use of artificial nutrition that uses the gastrointestinal tract, namely enteral nutrition (EN) and oral nutrition supplements.

METHODS

The literature review was based on searches of the Health Economic Evaluations Database (HEED) and the NHS Economic Evaluation Database (NHSEED), plus the Cochrane Database of Systematic Reviews. The 2 economic-evaluation databases searched consist of studies identified by thorough searches of larger databases such as MEDLINE, EMBASE, Current Contents and CINAHL, and through hand-searching journals, working papers, and technology assessment reports. Searches were conducted in February 2003 for references published from 1990 onwards. Studies suggested by referees were also reviewed for relevance.

Inclusion and Exclusion Criteria

The intention of the literature review was to focus on EN and oral supplements, rather than parenteral nutrition (PN). Therefore, studies that investigated PN alone were excluded. In some conditions, PN and EN may be considered as alternatives. For example, the clinical literature comparing EN vs PN in acute pancreatitis has been the subject of a Cochrane review.3 Studies in the current review were considered eligible for inclusion not only if they assessed the nutrition feeding itself but also the timing of nutrition (eg, early vs late), the setting (eg, home vs hospital), or mode of delivery (eg, with or without the use of a nutrition team). Nutrition interventions considered relevant were those dealing with a nutrition deficit as a result of a current health problem rather than, for example, use of calcium supplements to prevent fractures. Studies that focused on the mode of access for delivering a nutrition intervention were excluded.

Economic evaluations were included, that is, studies that undertook some assessment of the costs and outcomes (health effects) of 2 or more alternative interventions rather than reporting results from elsewhere. In addition, HEED includes cost analyses that compare the costs only of alternative interventions, and "costoutcome descriptions," which examine the costs and outcomes of an intervention but lack an explicit alternative against which it is compared. These were deemed eligible for inclusion. Studies that reported costs as items of resource use only, such as length of hospital stay, were excluded, as were cost-of-illness studies, which simply assess the total costs of a given disease.

Assessment of Study Quality

Study quality was assessed by one of the authors (CP) for the randomized controlled trials (RCTs) in the sample using the Jadad et al4 score and the BMJ checklist.5 A set of tables summarizes these quality assessments by type of intervention.

The Jadad score is based on the following 3 questions:

* Was the study described as randomized?

* Was the study described as double blind?

* Was there a description of withdrawals and dropouts?

A study scores 1 point for each "yes" and 0 points for each "no." For the first 2 questions, an additional point can be awarded or deducted, depending on the appropriateness of the randomization and blinding methods used. For each of these methods, an additional point is awarded if the method is described and is appropriate, but a point is deducted if the method is described but is inappropriate. The maximum possible score is therefore 5 points. The guidelines for assessment set out by the developers of the scale4 were followed when scoring studies.

The BMJ referees' checklist consists of 35 items in 3 summary categories: study design (7 items), data collection (14 items), and analysis and interpretation of results (14 items). "Yes,""no," and "not clear" responses can be recorded for each item, whereas, for some items, "not appropriate" can be recorded. For example, the statement "Details of any model used are given" would be "not appropriate" if no model had been used. Because each of the studies for which the checklist was completed was based on a single randomized trial, the statement "Details of the method of synthesis or meta-analysis of estimates are given" was recorded as "not appropriate" in each case. In contrast with the Jadad scale, the BMJ checklist does not have its own scoring system. Therefore, the tables in this paper report the number of times "yes,""no,""not clear," and "not appropriate" were recorded as a proportion of the number of items in each of the 3 summary categories of methods. The more frequently "yes" is recorded, the more thoroughly the authors of the study have addressed relevant aspects of methodology and the more comprehensively they have reported their methods.

Results by Type of Intervention

EN vs PN. Seven of the 19 studies in which a comparison of EN and PN patients was undertaken simply assessed what the costs would have been using PN rather than EN.6-12 Although these studies report lower costs for EN, there is a suggestion that the ratio between PN and EN costs may have fallen over time. A 1996 US study6 among pediatric intensive care unit (ICU) patients estimated a daily charge of $46 for EN compared with $471 for PN. In comparison, a 1999 US study11 among children with cancer estimated a total cost for the patient group treated with tube feeding of $25,348 compared with $112,299 for the same number of days of PN. This may be due in part to a fall in the relative price of PN but may also reflect variation in patient characteristics. For example, a study among trauma patients12 using pooled data on complications from randomized trials and US costs and prices estimated the cost of PN to be between 4 and 15 times that of EN.

The economic analyses based on observational nonrandomized studies comparing groups receiving EN and PN13-16 found few differences in clinical outcomes between groups but again reported lower costs in EN patients. All studies were simple retrospective reviews, and the findings could have been influenced by study design.

For the 9 RCTs listed in Table I, there was a tendency again to report costs in terms simply of daily costs for nutrition support. In 19 US patients about to undergo major abdominal surgery,17 mean daily costs for EN were just under half the corresponding cost of PN of around $100 per day, whereas, in 24 UK patients undergoing primary orthotopic liver transplantation,18 a 10-fold difference was reported (7 per day vs 75-85). Neither study was able to detect a significant difference in clinical outcomes, and, in the latter study, no significant difference was reported in length of hospital stay (32 vs 31 days in PN and EN groups, respectively). Length of stay was also comparable between EN and PN groups (40 vs 39 days) in a Greek study of 40 enrolled patients with acute severe pancreatitis, despite fewer complications being observed in the EN group.19 Costper day was put at 30 for EN and 100 for PN.

A similar ratio of costs per day was reported in 2 other studies. The largest of the randomized trials comparing early EN and PN,20 among 257 patients with cancer of the upper gastrointestinal tract, found no significant difference in clinical variables between patient groups but a significantly shorter length of hospital stay for early EN (19.8 days vs 22.6 days). A Finnish study21 in 29 patients undergoing total gastrectomy for gastric carcinoma reported the costs of 5 days' feeding in each group; only 1 measure of safety and tolerability differed significantly between groups. Another variation on the costing method was to report costs for a "typical" patient.22 In 59 patients with head injuries in a US trauma center, the costs of 10 days' PN followed by gastric feeding were estimated to be similar to those of EN alone (around $2000-$3000). The incidence of occurrences of hyperglycemia and of diarrhea which have economic implications favored the EN group.

TABLE I

RCT study quality: enteral nutrition vs parenteral nutrition

Two RCTs from the United States and 1 from Canada reported per- patient costs, with each study being conducted in patients with pancreatitis. In 53 US patients with acute pancreatitis,23 hyperglycemic and line-infection rates were higher for PN patients, whereas average per-patient nutrition costs were significantly lower in the EN group at $394 as opposed to $2756 for PN patients. Hospital stay was shorter in the EN group (12.8 vs 20.1 day), again suggesting an economic benefit. In the smaller of the 2 US studies, of 32 admissions for acute pancreatitis or an acute flare-up of chronic pancreatitis,24 the investigators found no significant difference in clinical endpoints, whereas mean costs of nutrition support (based on patient charges) were $761 compared with $3294 in EN and PN groups, respectively. Finally, a Canadian study in severe pancreatitis, reported in abstract form,25 found a nonsignificant difference between the average cost for the 10 patients randomized to total EN ($1207) and that for the 15 patients randomized to PN ($1968), confirming the trend observed in previous studies.

EN vs Standard Care. Of the 5 studies comparing EN with no nutrition intervention, 3 collected primary data alongside an RCT. However, these were all of low internal validity (Table II). In a small UK trial26 that enrolled 30 patients undergoing laparotomy for chronic gastrointestinal disease, protein and energy intake and attenuation in gut permeability improved significantly in those receiving enteral feeding at a cost of 12 per day compared with 3 per day for those randomized to IV fluids. Two patients who did not proceed to resection (1 in each group) were excluded from the analysis. A US study27 randomized 50 liver transplant patients to enteral feeding or IV fluids. However, the analysis was restricted to 31 patients who completed the study over the first 21 days after transplantation. Among these patients, 1 measure of nutrition outcome (speed of nitrogen balance recovery) favored the enteral feeding group, whereas there was no significant difference in initial hospital charges (which include the cost of feeding) in the tube-fed and nontube-fed patients ($93,857 vs $94,916). In a Danish study28 of 60 patients receiving either EN or placebo after major abdominal surgery, postoperative complications were lower in the EN group. Median cost per patient was lower in the EN group, although, as we are concerned with total costs in economic evaluation, it would have been more appropriate to report mean costs, which have a direct relationship to total costs.29

Evidence on complications in patients receiving perioperative EN has been drawn from trial results and combined with literature- based cost data.30 Using assumptions about hospital bed costs, duration of preoperative EN, daily costs of EN, reduction in the rate of postoperative complications, and compliance rates, the authors estimated a cost per complication avoided of $9000 for EN. Separate estimates were derived for patients with hip fracture, giving a breakeven point for ONS if daily hospitalization costs were in excess of $240.

TABLE II

RCT study quality: enteral nutrition vs standard care

For patients undergoing bowel resection, general surgeons were given the opportunity to participate in the delivery of early enteral feeding in a US observational study.31 In 66 patients treated by participating surgeons, there was a significant reduction in nosocomial bacteremia compared with the 159 patients treated by nonparticipating physicians and a significant cost reduction of $4450 per successfully treated patient (patients discharged from the hospital without a complicating infection).

Immunonutrition

All 4 studies of immunonutrition identified in Table III were based on randomized trials among patients undergoing surgery for malignancies of the gastrointestinal tract. An Italian study32 of 206 enrolled patients and a German study33 of 164 enrolled patients compared an enteral enriched diet with an isonitrogenous isocaloric control postoperatively. Both studies found that costs of immunonutrition were more than offset by reduced costs of complications. In the former, a significant reduction in the number of complications resulted in a mean cost for nutrition and complications of euro1115 per patient in the treatment group and a corresponding cost of euro2447 in the control group. In the German study, although the prevalence of complication events overall was not significantly different between the 2 groups, a cost saving of 23,248 Marks was reported for the 77 patients receiving immunonutrition.

TABLE III

RCT study quality: immunonutrition

A second German study34 randomized 178 patients (154 of whom completed the study) to immune-enhancing feeding or an isoenergetic control administered preoperatively and postoperatively. Significantly fewer patients in the immune-enhancing feeding group developed complications after postoperative day 3, and the mean per- patient costs of nutrition and treating complications were lower in this group at 1311 deutschemarks compared with 2737 Marks in the control group.

A US study35 randomized 136 patients to immuneenhancing feeding or standard formula delivered either preoperatively and postoperatively or postoperatively alone. Patients receiving immune- enhancing nutrition were found to experience a significantly reduced rate of postoperative infection, but their length of stay was not significantly different from standard formula patients. No direct per-patient cost comparisons are presented, but the authors estimate that immune-enhancing nutrition could generate cost savings through reduced hospitalization well in excess of the costs of the nutrition supplement.

TABLE IV

RCT study quality: glutamine supplements

Glutamine Supplements

The 2 randomized trials of glutamine supplements in our sample were among the higher-quality studies, as measured by the Jadad score (Table IV). One was a US study that enrolled 68 premature infants36 in the neonatal ICU, and the other was a UK study that recruited 78 adult patients admitted as emergencies to the ICU.37 The first of these cited a previous trial report as showing a lower incidence of hospital-acquired sepsis and improved tolerance to enteral feeding with the nutrition supplement compared with the control feed. For each category of resource use, median costs were significantly lower in the supplement group. For the 50 patients who successfully started enteral feeding in the UK study, there was no significant difference in 6-month survival between glutamine- supplement and control-feeding patients. The analysis showing that costs of ICU and post-ICU hospital stay were significantly lower in those receiving the supplement was again inappropriately based on the median. However, using the total ICU and post-ICU costs, mean per-patient costs were found to be $23,585 and $36,884 in the supplement and control groups, respectively.

Other Supplements

Two articles have provided evidence on branched-chain amino acids (BCAA) in patients with liver disease. One report38 noted the results of a randomized trial showing a significant reduction in mortality at year 4 (but not year 5) compared with an isocaloric isonitrogenous control group and presented costs per L for a range of enteral formulas, that of BCAA being 10 times that of the others. In the other report,30 modeling was used to estimate the cost- effectiveness of BCAA vs lactulose in patients with hepatic encephalopathy. Different scenarios were explored, but, although BCAA was the more costly option, no evidence of greater benefit was provided. The same authors report their own modeled estimates of the cost-effectiveness of 6-mercaptopurine vs elemental diet (ED) in steroid-refractory Crohn's disease.30 Costs were greater for ED patients, but it is unclear whether a greater benefit can be expected.

TABLE V

RCT study quality: oral nonimmune-enhancing supplements

The use of ornithine oxoglutarate (OGO) has been investigated in a well-designed French placebo-controlled trial (Table V) that enrolled 194 elderly patients recovering from acute illnesses.39 Significant improvements in a number of outcome measures, including a quality-of-life index, in the OGO group compared with the placebo group were accompanied by a reduction in costs (2586 us 4089 French francs).

Two UK studies have investigated the use of ONS in surgical patients. In one,40 54 patients scheduled to undergo moderate to major gastrointestinal procedures were randomized to receive a normal ward diet postoperatively or the same diet supplemented by ONS. The analysis, based only on the 40 patients who completed the trial, showed statistically significant differences in favor of treatment for handgrip strength and incidence of serious complications. The cost of treatment was expressed \merely as a daily figure (2) and compared with corresponding daily costs of EN (10) and PN (55). In the second study, reported in abstract form,41 179 patients undergoing lower gastrointestinal surgery were randomized to nutrition supplementation (NS) presurgery, postsurgery, pre- and postsurgery, or no NS. Analysis of 152 of these patients found a significantly lower rate of minor complications in postsurgery only and pre- and postsurgery groups compared with the no-NS group; per-patient costs did not differ significantly between groups.

Nutrition Support Teams (NSTs)/Protocols

Evidence on the cost impact of NSTs or nutrition support protocols was limited to observational studies. A reported of an experience in a Spanish hospital42 suggested that the NST could reduce costs by recommending a switch from PN when oral or enterai feeding routes are available. A US study assessing the impact over time of the introduction of a nutrition protocol43 found improvements in the appropriateness of nutrition interventions, with an increase in enteral feeding, a reduction in PN, and corresponding cost savings.

Two studies have assessed patient outcomes and costs in a US setting. In a comparison of NST and nonteam management,44 average complication rates were significantly lower for NST patients but not mortality rates adjusted for disease severity. Although adjusted length of stay did not differ significantly between groups, the magnitude of the difference in length of stay was used to estimate a saving of >$4 for every $1 invested in the NST. Reduced length of stay, along with an improvement in mortality for patients receiving early enteral feeding, was also cited as a source of cost savings in a study45 of educational and other measures to meet a range of nutrition objectives (including initial use of EN rather than PN in the ICU).

DISCUSSION

Quality of Studies

Overall, 16 of the 21 randomized trials in our sample scored <3 on the Jadad scale, including all studies of EN vs PN, and therefore could be regarded as being of poor quality.46 Other drawbacks with studies not accounted for in the Jadad score were small sample size and a failure to analyze on an intention-to-treat basis (or a lack of clarity in how the data had been treated). For example, the analysis of one glutamine trial37 was limited to successfully treated patients, and the 2 UK-based trials of oral supplements40,41 failed to include all randomized patients in the analysis. Although the largest of the immunonutrition trials reported its results on an intention-to-treat basis, the 2 intermediate studies used an as- treated analysis. Moreover, although all trials of this therapy stated that they were blinded, none of them commented on any measures they had taken to disguise the odor of the immune- enhancing supplement.

As far as the status of studies as economic analyses is concerned, the BMJ checklist does not generate an overall score, but it did serve to highlight some of the weaknesses with the trial- based studies. For the 7 items in the study design section, it was usual for a minority of items to be addressed. This reflected a failure, for example, to state the viewpoint of the analysis or to state or justify the form of economic evaluation used.

The same was true of the 14 items in each of the "data collection" and "analysis and interpretation of results" categories. The number of no responses was frequently due to the lack of detail provided for the cost estimates; for example, a failure to report quantities of resources and unit costs separately or to explain the methods used to estimate costs. "Not appropriate" had to be recorded for many items because they asked about the basis for an analysis that had not been performed; for example, methods to value health states (no study used utility assessment). Although studies may have investigated relevant comparators, it was unclear whether it might also have been appropriate to include a broader set of comparators.

In general, costing methods were crude, and it appeared that costs were far from comprehensive. Generally, they appeared to be reported for the nutrition supplements, and then often on the basis of a daily rate, rather than full costs of treatment. In some cases, median, rather than mean, costs were reported. On the outcomes side, there was a failure to measure final endpoints rather than intermediate clinical endpoints.

Many of the "not appropriate" entries recorded for the items relating to "analysis and interpretation of results" related to a failure of the trial-based studies to make even a minimal allowance for uncertainty by the use of sensitivity analysis. Nor did authors take advantage of the stochastic nature of the data to present measures of precision such as confidence intervals.

Limitations of the Review

Although we took a broad view of what constituted an economic evaluation, we limited the age of studies we considered to those published from 1990 onwards. The basis for this is that methods and practical application of economic appraisal have developed considerably over time, and therefore older studies are likely to be of limited relevance compared with more recent studies. Our approach was also consistent with the bulk of the coverage of the 2 economic evaluation databases we searched, HEED and NHSEED. However, an alternative approach would have been to take a longer historical perspective but be more selective with regard to the studies included; for example, by excluding studies not reporting costs per patient. In addition, although we felt it unnecessary to search the main clinical databases, because these provide source material for HEED and NHSEED, the generic terms used to identify economic evaluations from databases such as MEDLINE and EMBASE may have missed some nutrition-specific references. As the basis for our assessment of study quality, we recognize that a points system such as the Jadad score (although widely used, including in a review of EN and PN in acute pancreatitis47) is an imperfect tool that needs to be supplemented with a consideration of other aspects of quality.

CONCLUSIONS

To our knowledge, this is the first systematic review of published economic evaluations on enteral nutrition, namely oral nutrition supplements and enteral tube feeding. The review identified very few nutrition studies with a health economics component. Of these studies, many were inadequately designed and collected rudimentary figures associated only with the cost of the nutrition intervention, rather than considering the wider economic benefits, such as an associated decrease in length of stay or reduction in infectious complications postoperatively. The lack of economic evidence for nutrition could in part be due to the ethical issues associated with conducting clinical studies in the area. The withholding of nutrition for the comparator is not feasible and the definition of this group remains a strong methodological challenge.

Considering only the randomized trials, the largest body of evidence was for the comparison of EN with PN. In the studies reporting mean costs per patient, costs were lower for EN patients, albeit perhaps limited to the costs of the supplements alone. The largest trial reported daily costs and found a shorter length of stay but no difference in clinical endpoints. Generally, there was either no difference in outcomes or the results favored the EN group.

A tentative conclusion would be that, for some patient groups for whom EN and PN are genuine alternatives, EN can be used with no clinical disadvantage but at lower cost. Comparisons of EN vs PN covered a diversity of patients groups, the one in which most randomized trials were found being acute pancreatitis (3 of 8 studies), an indication considered by previous reviews. Although a Cochrane review3 found insufficient evidence to draw firm conclusions about the effectiveness and safety of EN vs PN, an earlier review48 concluded that enterai feeding is preferable to the parenteral route in pancreatitis. None of the studies reviewed here made a direct comparison of EN, PN, and control, and the studies of EN vs control offer little on which to draw conclusions, although a study published since the current review was undertaken recommends EN as the preferred form of nutrition support in acute pancreatitis.47

Smaller in number but with greater patient enrollment than most of the trials of EN and PN were the trials of immune-enhancing supplements. Although these trials were not all analyzed on a comparable basis and the generalizability of their results may be questioned, the suggestion that immunonutrition in patients undergoing surgery for gastrointestinal malignancies can reduce complications and potentially costs is an important finding that merits further investigation.

The literature search conducted scaled the period from 1990 to 2003. The authors acknowledge that over this timescale clinical practice will have changed both in terms of nutrition and medical/ surgical interventions, some of which could have an economic impact. For example, the move from hyperalimentation to feeding to lower energy requirements will affect overall costs for both enteral and parenteral nutrition as smaller volumes of feeds are being prescribed. Hence the economic data presented is more illustrative of trends rather than actual cost savings.

A question that these studies, as others, raise is the extent to which it may be appropriate to compare a broad range of nutrition options in different groups of patients. Too little evidence of insufficient quality was identified here to say anything about the costs and effects of different types of nutrition intervention. The absence of evidence was particularly noticeable for nutrition supplements delivered in the community, only 1 trial meeting the criteria for inclusion in this review. Also, many of the economic studies identified were based in \the US and their generalizability to other countries where different healthcare systems exist could be questioned.49 For example, in some countries the funding arrangements for the hospital and community settings may be separate. However, even although there may be variation in pricing arrangements between healthcare settings, it is not to say that cost and health benefits of nutrition support will not be realized in both hospitals and the community.

Further research would be valuable to investigate the costs and effects of different forms of nutrition in different patient groups and to assess the role of NSTs and protocols. The inclusion of costs in trials of interventions can provide useful information but, as with the design of the studies themselves, should follow robust methods frequently lacking in this sample. Although there is a lack of well designed economic studies taking a broad view of relevant comparators, costs and outcomes, there is some evidence to indicate clinical and economic advantages of enteral over parenteral nutrition. Further economic studies, particularly for nutrition support in the community, are required.

ACKNOWLEDGMENTS

We are grateful to Dr Jon Shaffer for comments on a previous report based on this review and to 2 anonymous referees for comments on an earlier version of this paper. Any errors remain the responsibility of the authors. Funding was provided by Abbott Laboratories.

REFERENCES

1. National Institute for Clinical Excellence. The Guideline Development Process: An Overview for Stakeholders, the Public and the NHS. London, England: National Institute for Clinical Excellence; 2004.

2. National Institute for Clinical Excellence. Scope: Nutrition Support. London, England: National Institute for Clinical Excellence; 2003.

3. Al-Omran M, Groof A, Wilke D. Enteral versus parenteral nutrition for acute pancreatitis (Cochrane Review). The Cochrane Database of Systematic Reviews 2003, Issue 1, Art. No.: CD002837. DOI: 10.1002/14651858.CD002837.

4. Jadad AR, Moore A, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12.

5. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. BMJ. 1996;313: 275- 283.

6. Chellis MJ, Sanders SV, Webster H, Dean JM, Jackson D. Early enteral feeding in the pediatric intensive care unit. JPEN J Parenter Enteral Nutr. 1996;20:71-73.

7. DeSwarte-Wallace J, Firouzbakhsh S, Finklestein JZ. Using research to change practice: enteral feedings for pediatric oncology patients. J Pediatric Oncol Nurs. 2001;18:217-223.

8. Finocchiaro E, Alaria P, Galletti R, Balzola F. Economic evaluation of home enteral nutrition. RINPE. 1997;15:24-31.

9. Lobo DN, Sarkar AK, Marwaha N, Singh G, Khanna SK. Enteral nutrition in surgical patients. Natl Med J Ind. 1992;5:55-59.

10. Mercer CD, Mungara A. Enteral feeding in esophageal surgery. Nutrition. 1996;12:200-201.

11. Pietsch JB, Ford C, Whitlock JA. Nasogastric tube feedings in children with high-risk cancer: a pilot study. J Pediatr Hematol Oncol. 1999;21:111-114.

12. Trice S, Melnik G, Page CP. Complications and costs of early postoperative parenteral versus enteral nutrition in trauma patients. Nutr Clin Pract. 1997;12:114-119.

13. de Lucas C, Moreno M, Lopez-Herce J, Ruiz F, Perez-Palencia M, Carrillo A. Transpyloric enteral nutrition reduces the complication rate and cost in the critically ill child. J Pediatr Gastroenterol Nutr. 2000;30:175-180.

14. Pettignano R, Heard M, Davis R, Labuz M, Hart M. Total enteral nutrition versus total parenteral nutrition during pediatric extracorporeal membrane oxygenation. Crit Care Med. 1998;26: 358- 363.

15. Reddy P, Malone M. Cost and outcome analysis of home parenteral and enteral nutrition. JPEN J Parenter Enteral Nutr. 1998;22:302-310.

16. Reddy P, Malone M. Cost and outcome analysis of home parenteral and enteral nutrition [Abstract]. Pharmacotherapy. 1997; 17:1108.

17. Hamaoui E, Lefkowitz R, Olender L, et al. Enteral nutrition in the early postoperative period: a new semi-elemental formula versus total parenteral nutrition. JPEN J Parenter Enteral Nutr. 1990;14:501-507.

18. Wicks C, Somasundaram S, Bjarnason I, et al. Comparison of enteral feeding and total parenteral nutrition after liver transplantation. Lancet. 1994;344:837-840.

19. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg. 1997;84:1665-1669.

20. Braga M, Gianotti L, Gentilini O, Parisi V, Salis C, Carlo VD. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med. 2001;29:242-248.

21. Sand J, Luostarinen M, Matikainen M. Enteral or parenteral feeding after total gastrectomy: prospective randomised pilot study. Eur J Surg. 1997;163:761-766.

22. Borzotta AP, Pennings J, Papasadero B, et al. Enteral versus parenteral nutrition after severe closed head injury. J Trauma. 1994;37:459-468.

23. Abou-Assi S, Craig K, O'Keefe SJD. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol. 2002;97:2255-2262.

24. McClave SA, Greene LM, Snider HL, et al. Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis. JPEN J Parenter Enteral Nutr. 1997;21:14-20.

25. Louie B, Noseworthy T, Hailey D, Gramlich L, Jacobs P, Warnock G. A randomized controlled trial and cost effectiveness analysis of enteral vs. parenteral nutrition in severe pancreatitis. Gastroenterology. 2002;122:A-369.

26. Carr CS, Ling KDE, Boulos P, Singer M. Randomised trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection. BMJ. 1996;312: 869- 871.

27. Hasse JM, Blue LS, Liepa GU, et al. Early enteral nutrition support in patients undergoing liver transplantation. JPEN J Parenter Enteral Nutr. 1995;19:437-443.

28. Beier-Holgersen R, Boesby S. Influence of postoperative enteral nutrition on postsurgical infections. Gut. 1996;39:833-835.

29. Barber JA, Thompson SG. Analysis and interpretation of cost data in randomized controlled trials: review of published studies. BMJ. 1998;317:1195-1200.

30. Ofman J, Koretz RL. Clinical economics review: nutritional support. Aliment Pharmacol Ther. 1997;11:453-471.

31. Hedberg A-M, Lairson DR, Aday LA, et al. Economic implications of an early postoperative enteral feeding protocol. J Am Diet Assoc. 1999;99:802-807.

32. Gianotti L, Braga M, Frei A, Greiner R, Di Carlo V. Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition. Shock. 2000;14:325-330.

33. Senkal M, Mumme A, Eickhoff U, et al. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Crit Care Med. 1997;25:1489-1496.

34. Senkal M, Zumtobel V, Bauer K-H, et al. Outcome and cost- effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery. Arch Surg. 1999;134:1309-1316.

35. Snyderman CH, Kachman K, Molseed L, et al. Reduced postoperative infections with an immune-enhancing nutritional supplement. Laryngoscope. 1999;109:915-921.

36. Dallas MJ, Bowling D, Roig JC, Auestad N, Neu J. Enteral glutamine supplementation for very low-birth-weight infants decreases hospital costs. JPEN J Parenter Enteral Nutr. 1998; 22:352- 356.

37. Jones C, Palmer TEA, Griffiths RD. Randomized clinical outcome study of critically ill patients given glutamine- supplemented enteral nutrition. Nutrition. 1999;15:108-115.

38. Levinson MJ. A practical approach to nutritional support in liver disease. Gastroenterologist. 1995;3:234-240.

39. Brocker P, Vellas B, Albarede JL, Poynard T. A two-centre, randomised, double-blind trial of ornithine oxogluturate in 194 elderly, ambulatory, convalescent subjects. Age Ageing. 1994;23: 303- 306.

40. Rana SK, Bray J, Menzies-Gow N, et al. Short term benefits of post-operative oral dietary supplements in surgical patients. Clin Nutr. 1992;11:337-344.

41. Smedley F, Goodger C, Oldale C, James M, Jones P, Bowling T. Benefits of extended pre- and post-operative oral nutritional supplementation (NS); a prospective randomized controlled trial. Clin Nutr. 2002;21(suppl 11):39-40.

42. Balet A, Cardona D, Pasto L, Bonal J. Importance of a nutrition support team to promote cost containment. Ann Pharmacother. 1992;26:265.

43. Pace NM, Long JB, Elerding S, et al. Clinical research, performance model anchors successful nutrition support protocol. Nutr Clin Pract. 1997;12:274-279.

44. Hassell JT, Games AD, Shaffer B, Harkins LE. Nutrition support team management of enterally fed patients in a community hospital is cost-beneficial. J Am Diet Assoc. 1994;94:993-998.

45. Schwartz DB. Enhanced enteral and parenteral nutrition practice and outcomes in an intensive care unit with a hospital- wide performance improvement process. J Am Diet Assoc. 1996;96: 484- 489.

46. Jadad AR. Randomised Controlled Trials. London, England: British Medical Journal Books; 1998.

47. Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ. 2004;328:1407-1410.

48. McClave SA, Ritchie CS. Artificial nutrition in pancreatic disease: what lessons have we learned from the literature? Clin Nutr. 2000;19:1-6.

49. Drummond M, Pang F. Transferability of economic evaluation results. In: McGuire A, Drummond M, eds. Economic Evaluation in Health Care: Merging Theory with Practice. Oxford, England: Oxford University Press; 2002:256-276.

Clive Pritchard, PhD*; Steven Duffy, PGDip[dagger]; Jackie Edington, PhD[double dagger]; and Francis Pang, PhD

From the * Office of Health Economics, London, \England; [dagger] NHS Centre for Reviews and Dissemination, University of York, York, England; [double dagger] Orion Technology, Gerrards Cross, Buckinghamshire, England; and Abbott Laboratories UK, Abbott House, Berkshire, England

Received for publication July 30, 2004.

Accepted for publication September 15, 2005.

Correspondence: Clive Pritchard, Office of Health Economics, 12 Whitehall, London SW1A 2DY, England. Electronic mail may be sent to cpritchard@ohe.org.

Copyright American Society for Parenteral and Enteral Nutrition Jan/ Feb 2006

Source: JPEN, Journal of Parenteral and Enteral Nutrition

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