Approach to Oral and Enteral Nutrition in Adults

Topic 8

Module 8.2
Oral and sip feeding
Marian van Bokhorst de van der Schueren
Kristina Norman
Learning Objectives

To be aware of the importance of optimal nutrition in hospital patients;

To know about the different menus and possibilities of fortification offered by the
average hospital food service;
To learn about innovative approaches to increase nutritional intake of normal food in
hospital patients;
To know the indications for and types of oral nutritional supplements;

Contents
1.
2.
3.
4.
5.
6.
7.

Why is oral nutrition important in hospital patients?

Requirements of oral nutrition in hospital
Monitoring and improving oral intake
Fortification of standard hospital food and oral supplements (sip feeds)
When to administer oral supplements
Summary
References

Key Messages

Oral feeding with either normal food or special and/or fortified diets is always the first
choice to prevent or treat undernutrition in patients;
Food served in hospitals should be a role model for food at home, i.e. should have a
high quality in terms of nutritional physiology, raw materials and preparation and
should be attractive in taste and appearance;
The quantity of oral intake must be carefully monitored, especially in patients at
nutritional risk;
Sip feeding (oral nutritional supplements) should be used when adequate oral intake
of normal food including special and/or fortified diets is not possible.

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1. Why is Oral Nutrition Important in Hospital Patients?
Good and nutritious food is a major contributor to quality of life and wellbeing.
Oral nutrition with normal food should therefore always represent the first-line dietary
measure for patients who are able to eat in order to prevent or correct malnutrition.
Hospital food must consequently meet several requirements. In order to provide the
patients with all necessary macro- and micronutrients, it should have a high quality in
terms of nutritional physiology, raw materials, hygiene and preparation. It must be
attractive in both taste and appearance. The temperature of food served hot is also of
central importance (6070 C), especially for slow eaters and those who need help to eat
(1)).

2. Requirements of Oral Nutrition in Hospital

The macronutrient ratio of the standard hospital food (general menu), for hospital
patients not at risk of malnutrition, corresponds to the requirements of optimal nutrition
and should consist of 45-55% carbohydrate (of which 20-30 grams fibre), 30-35% fat
and 15-20% protein. Twenty-five percent of the energy should be provided at breakfast,
30% at lunch and 25% in the evening. The remaining 25% should be distributed over the
day in form of snacks.
Macronutrient ratios, meal patterns and menus (including medically indicated diets) vary
between European countries. Most countries have issued national recommendations,
either at governmental level or based on guidelines by clinical nutrition societies (see the
Resolution on Food and Nutritional Care in Hospitals of the Council of Europe) (2).
In addition to the normal diet a variety of menus targeted to specific patient categories
and needs must be available in hospital, such as diets for medical indications (e.g. diets
with defined protein and electrolyte content, texture modified diets for patients with
chewing and swallowing problems, as well as energy- and protein-dense diets aimed at
patients at risk or with disease related malnutrition).

Hospital menus

Standard diet
Protein/energy enriched diets
Restricted diets (e.g. electrolyte restriction in
case of kidney failure, energy restriction in
case of obesity)
GI diets (lactose free, gluten free, diets for
malabsorption,
malabsorption, e.g. semisemi-elemental or diets
based on medium chain triglycerides)
Diets for metabolic disorders (e.g. metabolic
disorders in children such as
phenylketonuria)
phenylketonuria)

Figure 1 Hospital menus

Since it might be difficult to take all religious or individual dietary regulations into
account, vegetarian dishes must be offered as a possible alternative.
Indications must be well grounded if dietary restrictions are instituted for medical
reasons, since undernutrition can result from unnecessarily restrictive diets (Fig 1) (3).
Mealtimes:

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Serving hours should be planned to allow sufficient time between each meal for inbetween snacks in the morning, afternoon and late evening. Bearing in mind that nil by
mouth periods and diagnostic examinations frequently collide with the appointed meal
times, in-between snacks and nourishing drinks should be available to the patients on all
wards and also offered when appropriate in order to enhance nutritional intake. Every
effort should be made in order to minimize interruptions of meal times.
Patients should be able to choose from a menu which is in accordance with their age,
religious and cultural background, and should receive help and guidance in choosing the
food from the ward staff if necessary.
Patients should be able to order extra food at any time and should be informed of this
possibility.
Feedback from patients to the ward and to the kitchen regarding dislike or appreciation
of the served food should be encouraged.

3. Monitoring and Improving Oral Intake

Taking into account that food intake in hospital is frequently suboptimal (4) and that
malnutrition usually worsens during hospital admission (5-8), every effort should be
made to ensure appropriate nutritional intake (Fig 2).

Figure 2 Food intake in hospital

One novel way of ensuring at least thirty minutes of undisturbed meal time, is the
protected meal times policy which has been promoted by the British Hospital Caterers
Association (HCA). The protected meal time requires the minimisation of interruptions
such as medical or drug rounds or cleaning, and the rescheduling of procedures to avoid
the three appointed meal times. Nursing staff are then able to provide assistance and
encouragement to eat where necessary, and will then have immediate knowledge of
patients eating habits or difficulties. (Fig. 3)
Other solutions to improve intake include: tailoring food provision to meet the demands
of the patients (i.e. guaranteeing that the hospital meals meet the requirements of
patients)(9), having patients make their food choice at the point of consumption , for
example by changing food catering from plated systems (ordering choices and portion
size in advance) to a bulk system (ordering at the moment of consumption) (10;11).

Enhancing nutritional intake I

Protected mealtimes: 3 mealtimes free
from avoidable and unnecesary
interruptions
InIn-between snacks
Food provision tailored to patients
patients
requirements
Food choice at point of consumption
Change from plated system to bulk
system

Figure 3 Enhancing nutritional intake

Monitoring nutritional intake is mandatory for early detection of patients who are at
nutritional risk. In a cross-sectional study by Hiesmayr et al. an association has been
shown between intake at mealtimes and clinical outcome (Fig 4) (12).

Impact of anorexia on mortality

Have you lost weight unintentionally
within the last 3 months?

How well have you eaten

during the last week?
12
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12

Hiesmayr M et al. Clin Nutr 2009; 28:484-91

Figure 4 Association between intake at meals and clinical outcome

Therefore supervision of tray collection is a first line measure to learn about patients
food intake, which should be noted with a semi-quantitative system. This could be done
easily by a simple registration system (Fig 5).

Easy meal registration

Register amount eaten from meals

Register in-between
meals

Figure 5 Example of simple meal registration

If a patient is at risk of malnutrition and is receiving nutritional therapy of any kind, food
intake should be registered more intensively with proper dietary records, for example by
24 hour recalls. Data from either kitchen or menu nutrient databases regarding energy
and protein content of hospital food and portion size should be available to each ward in
order to aid nursing staff in the assessment of patients food intake. The quantity of the
nutritional intake should be used to calculate the patients needs for further nutritional
support.

4. Fortification of Standard Hospital Food and Oral Supplements

(sip feeds)
Fortification: If patients are at nutritional risk and food intake is insufficient, fortification
of hospital food can be considered in order to improve nutritional intake. Protein can be
added in powder form, and adding fat (cream, butter, oil) or carbohydrates
(maltodextrins, dextrose) are simple ways to enhance the energetic value of food.

Enhancing nutritional intake II

Fortification of hospital food
Protein: powder
Fat: cream, butter, oil
Carbohydrates: maltodextrins,
maltodextrins, dextrose
Oral supplements (sip feeds)

Figure 6 Enhancing nutritional intake II

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By adding these components to the food, there is naturally a sensoric limitation to the
amount of additional energy or protein that can be achieved. Several studies have
however shown that enriching food leads to improved nutritional intake in elderly
patients who do not manage large amounts of food (13;14).
In patients who are not able to eat unaided but able to digest food, feeding assistance is
essential and should not routinely be replaced by artificial nutrition support (Fig. 6).
Oral supplements: If a patients nutritional status does not stabilise or improve after
fortification, oral nutritional supplements should be considered. There is a variety of oral
nutritional supplements:
Liquid/semi-solid supplements: Energy and protein enriched / liquid (milk based) sip
feeds: generally used as supplements, they can be used as a sole source of nutrition if
they are nutritionally complete. Also available with fibre.
Energy rich, normal or low protein / liquid (milk based or juice based): to be used as an
additional supplement, for example for patients with a (moderate) protein restriction.
Also available with fibre.
Protein enriched, normal in energy / liquid (milk based) or semi solid: for patients with
increased protein requirements. Depending on the brand also suitable as a complete
source of nutrition.
Concentrated sip feeds / liquid (milk based), typically > 2kcal/mL: high in energy and
protein in a smaller volume. Can be used as additional supplement or as complete source
of nutritional intake. Also available with fibre.
Semi solid / pudding-like: useful for dysphagic patients. Depending on the brand also
suitable as sole source of nutrition
Liquid sip feeds are generally available composed as follows:
Energy enriched:
Macronutrient ratio: 15 18 % protein, 30 35 % fat and 50 55 % carbohydrates
Energy and protein rich:
Macronutrient ratio: 25 - 30 % protein, 20 -25 % fat and 50 55 % carbohydrates.
Protein rich: 25 - 30 % protein, 30 % fat and 40- 45% carbohydrates
Powdered and liquid supplements. Powdered supplements: not suitable as sole
source of nutrition. Powdered feeds can be prepared with different consistencies which
might be useful for patients with dysphagia.
Energy supplements: not suitable as sole source of nutrition. Carbohydrate can be used
in patients who need extra energy. Available as powder (to be added to liquids), or as
liquid supplements. Fat emulsions (liquid) can be used for patients who need extra
energy;
Disease specific supplements
The market for disease specific supplements is growing fast.
Among disease specific products are:
- products based on short-chain peptides or amino-acids: for patients with
malabsorption (sometimes also enriched with glutamine or arginine)
- diabetes specific products for optimal glucose regulation (no mono- or
disaccharides, rich in mono-saturated fatty acids)
- products for patients with pressure sores: containing extra vitamins and minerals,
anti-oxidants and zinc
- products for cancer patients: usually containing omega-3-fatty acids and
antioxidants
- low fat products, containing medium chain triglycerides: for patients with
malabsorption
- carbohydrate rich supplements: to be used shortly before an operation
- immune enhancing products: often containing omega-3-fatty acids, arginine, RNA
nucleotides
- products for patients with pulmonary disease: low in fat, high in carbohydrates
and protein
- protein-restricted, electrolyte restricted, energy-enriched products: for patients
suffering from renal diseases

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products to slow down the progression of Alzheimers disease: containing omega3-fatty acids, anti-oxidants, B vitamins, choline and uridine monophosphate
- products to support elderly / geriatric patients: enriched in vitamin D, protein,
folic acid, etc.
Some of these supplements are also designed to cover daily requirements of macro- and
micronutrients.
-

Types of supplements
Liquid / semisemi-solid supplements:
Energy rich
Protein rich
Energy and protein rich

Powders and liquids:

Supplements containing proteins, carbohydrates and fats
Carbohdrates only (powder or liquid)
Fats only (liquids)

Disease specific products:

Cancer, renal disease, pulmonary disease
Immune enhancing
For patients with malabsorption,
malabsorption, diabetes, pressure sores

Figure 7 Types of supplements

5. When to Administer Oral Supplements

When patients cannot meet their nutritional requirements with standard hospital food or
enriched diets, supplementation with sip feeds must be considered.
Oral supplements should always be the first choice over enteral tube feeding, provided
that there are no swallowing difficulties and no obstruction in the oesophagus or
gastrointestinal tract. Oral sip feeding is not invasive and has no major side effects such
as the nasopharyngeal complications that may occur with nasogastric tubes. Moreover
salivary secretion with its antibacterial properties is stimulated.
In patients with no signs of malnutrition and no catabolic disease, oral supplementation
should start immediately if food intake is <60% of required intake during an actual or
anticipated period of 5-10 days, whereas malnourished patients or patients suffering
from severe catabolic disease with an anticipated reduced intake must be offered sip
feeds immediately. In case of weak and severely malnourished patients where even the
intake of oral supplements is not likely to cover requirements, tube feeding or parenteral
nutrition must be considered from the beginning.
There are moreover cases when supplements should be used first line, such as in tumour
patients before major surgery, in patients with malabsorption disorders or as adjuvant
therapy.
In Crohns disease, oral/enteral nutrition has also been proven to be effective for the
maintenance of remission (15).
For patients with advanced cancer and ongoing weight loss oral supplements containing
2-3 grams eicosapentaenoic acid (EPA) could be considered; these supplements are
thought to maintain weight and to improve quality of life. However they do not influence
morbidity or mortality. Figure 8 gives an overview of EPA studies and their results.

EPA studies in patients with cancer

Study

n, time, dose

Body weight

FFM

QoL / Survival

Takatsuka 2001
Single blinded

n=16 BMT pts, 180 d

1.8 g EPA (capsules)

Survival +
Morbidity (GvHD) -

Gogos 1998
Single blinded

n=60 cancer, 40 d
3.1 g EPA, 2.0 g DHA
(capsules)

Survival +
Performance +

Bruera 2003
Single blind

n=60, 14 d
Cancer (capsules)

QoL =

Fearon 2006
Double blinded

n=429 GI and lung ca, 8 wk

2 g EPA vs 4 g EPA vs 0 g

+ (trend 2 g
EPA)

Survival =
Physical function +(trend)

Fearon 2003
Double blinded

n=200 pancreatic ca, 8 wk

=
Post hoc: +

=
Post hoc: +

Survival =
QoL / Performance =

Moses 2004
Double blind

n=24 pancreatic ca, 8 wk

2.2 g EPA, 0.96 g DHA

Survival =
Physical activity level +

Guarcello 2007
Non-blinded

n=46 lung ca, 60 d

2.2 g EPA, 0.96 g DHA vs

+*

QoL +*

Bayram 2009
Non-blinded

n=52 children ca, 3 mo

2.2 g EPA, 0.96 g DHA vs
no suppl

Remission rate +

v.d. Meij 2010

Double blinded

n=40 lung ca, 5 wk

2.2 g EPA, 0.96 g DHA vs

QoL / Performance +
Physical activity +

* Within-group increase (P<0.05 vs. T0)

Figure 8 EPA studies in patients with cancer

There is enough evidence that patients undergoing major surgery of the upper
gastrointestinal tract will benefit from oral supplementation with immune modulating
substrates (arginine, omega-3-fatty acids and nucleotides; i.e. immunonutrition) for a
period of 5-7 days, independently of their nutritional status (both well-nourished and
malnourished) (16-18).
In radiotherapy patients, there is a body of evidence that nutritional support is of benefit.
Van den Berg et al. showed less weight loss in radiotherapy patients receiving nutritional
support than in those without (19). Also Isenring studied head and neck cancer patients
and observed smaller deteriorations in weight in patients receiving nutritional
counselling, compared to controls (20). The studies by Ravasco confirm earlier studies in
observing increased intake in head and neck or colorectal cancer patients undergoing
radiotherapy and receiving nutritional support (21;22). Again in head and neck cancer
patients, Wood et al. observed less weight loss in patients referred to a dietitian than was
seen in a historical control group (23).
Finally, Elia et al., in their systematic review, showed a significantly increased intake in
patients receiving oral nutritional supplements (all types of cancer) (24).
Effectiveness of oral supplements in enhancing nutritional status:
A meta-analysis dating from 1998 (25) on protein energy supplementation in adults
which analyzed results from 30 randomized controlled trials involving 2062 patients
demonstrated that nutritional parameters improved in the supplemented patients.
Seventeen of the trials used oral supplementation, and mean body weight improvement
in the treated groups was 2.39% (95% CI 2.43-3.89%) and the odds ratio for death in
those taking supplementation was 0.58 (95% CI 0.39-0.87%). However the authors
concluded similarly to the authors of a systematic review from 2001 (26) on treatment of
protein energy malnutrition in non-malignant disease, that further larger trials are
needed to provide a firm scientific basis for recommendations on how and when
nutritional supplements should be administered in certain diseases. A recent Cochrane
Review by Milne et al. (27), evaluating the effects of protein and energy supplementation
in 10,187 elderly people at risk of malnutrition, concludes that supplementation produces
small but consistent weight gains. In addition it may reduce mortality in older people.
However, most included trials were of poor quality. Additional data from large-scale

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multi-centre trials are still required. Baldwin compared dietary advice to nutritional
supplements and concluded that nutritional supplements may be more effective than
dietary advice (28). Ravasco also showed that the combination of nutritional support and
dietetic counselling was more effective than nutritional support alone (Fig 9).

Benefits of Nutritional Counselling on

Protein Intake During XRT

Ravasco P et al, JCO 2005; 23: 1431-8

Protein intake patterns during intervention and follow-up for three colorectal cancer study groups; G1=dietary
counselling, G2=supplements, G3=ad libitum intake. **G1~G2>G3 (p=0.006) and G1>G2~G3 (p=0.001)

Figure 9 Benefits of nutritional counselling during radiotherapy (XRT)

Choice of product:
Apart from the medical indications, the choice of product depends on its nutritional
profile, and its palatability and acceptability by the patient. Since good compliance is
essential to the success of the nutritional therapy, patient preference is vital. Earlier
studies have shown that enhanced compliance may be reached when the patients receive
a combination of supplements and counselling, instead of supplements only (29;30).
Once a product is chosen, compliance is enhanced through offering a variety of flavours.
Also, varying the form of intake can improve compliance (e.g. milk-based sip feeds
should be served cold, but can be added to fruits or dishes, frozen into ice creams or
diluted with milk).
Patients should however be counselled on the intake of the sip feeds. In order to avoid
side effects such as diarrhoea, constipation, nausea, oral supplements should be sipped
slowly. Also they should not be consumed before a meal, but between meals ( 1 hour
before) in order to increase energy consumption and avoid premature satiety (31).
Monitoring:
Nutritional therapy with oral supplements must be planned and supervised. Patients
compliance and weight changes must be monitored. If appropriate the therapy should be
adjusted on at least a weekly basis taking into account patients nutritional intakes,
weight change and relevant clinical parameters.
It is important that the intake of oral supplements does not decrease normal food intake,
so dietary food records should be kept.
The amounts of oral supplement should normally account for the missing energy and
protein that the patient is not able to consume with oral food intake alone.

6. Summary
Oral nutrition with normal food should be considered the first dietary measure to prevent
or treat malnutrition. Therefore a variety of menus for specific patient categories as well
as adequate choices for age, religious and cultural background should be provided.

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Appropriate nutritional intake should be assured with measures such as the protected
mealtimes policy or other measures to enhance nutritional intake. Monitoring nutritional
intake is mandatory for early detection of patients who are at nutritional risk.
If patients are identified as being at nutritional risk or malnourished their food can be
fortified to improve nutritional intake by adding protein, fat and carbohydrates. If the
problem is an inability to feed themselves, they can be given feeding assistance. If those
actions do not ameliorate the situation, supplementation with sip feeds should be
initiated. In case of weak or severely malnourished patients, where intake of oral
supplements is not likely to cover requirements, tube feeding or parenteral nutrition
must be considered from the beginning. The choice of supplement depends on the
nutritional profile and its acceptability to the patient. Good compliance is essential to the
success of nutritional therapy.

7. References
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(2) Committee of Ministers CoE. Resolution ResAP (2003)3 on food and nutritional care in
hospitals. 2003.
(3) Buckler DA, Kelber ST, Goodwin JS. The use of dietary restrictions in malnourished
nursing home patients. J Am Geriatr Soc 1994 Oct;42(10):1100-2.
(4) Barton AD, Beigg CL, Macdonald IA, Allison SP. High food wastage and low nutritional
intakes in hospital patients. Clin Nutr 2000 Dec;19(6):445-9.
(5) McWhirter JP, Pennington CR. Incidence and recognition of malnutrition in hospital.
British Medical Journal 1994;308:945-8.
(6) Pichard C, Kyle UG, Morabia A, Perrier A, Vermeulen B, Unger P. Nutritional
assessment: lean body mass depletion at hospital admission is associated with an
increased length of stay. Am J Clin Nutr 2004 Apr;79(4):613-8.
(7) Fettes SB, Davidson HI, Richardson RA, Pennington CR. Nutritional status of elective
gastrointestinal surgery patients pre- and post-operatively. Clin Nutr 2002
Jun;21(3):249-54.
(8) Bavelaar JW, Otter CD, van Bodegraven AA, Thijs A, van Bokhorst-de van der
Schueren MA. Diagnosis and treatment of (disease-related) in-hospital malnutrition: the
performance of medical and nursing staff. Clin Nutr 2008 Jun;27(3):431-8.
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Clin Nutr 2008 Dec;27(6):800-5.
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hospital: comparison of patients' satisfaction. Nutrition 2007 Mar;23(3):211-8.
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(12) 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
NutritionDay survey 2006. Clin Nutr 2009 Oct;28(5):484-91.
(13) Barton AD, Beigg CL, Macdonald IA, Allison SP. A recipe for improving food intakes
in elderly hospitalized patients. Clin Nutr 2000;19(6):451-4.
(14) dlund Olin A, Osterberg P, Hadell K, Armyr I, Jerstrom S, Ljungqvist O. Energyenriched hospital food to improve intake in elderly patients. JPEN J Parenter Enteral Nutr
1996;20(20):93-7.
(15) Akobeng AK, Thomas AG. Enteral nutrition for maintenance of remission in Crohn's
disease. Cochrane Database Syst Rev 2007;(3):CD005984.
(16) Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with
key nutrients in patients with critical illness and cancer: a meta-analysis of randomized
controlled clinical trials. Ann Surg 1999 Apr;229(4):467-77.
(17) Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition
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(18) Waitzberg DL, Saito H, Plank LD, Jamieson GG, Jagannath P, Hwang TL, et al.
Postsurgical infections are reduced with specialized nutrition support. World J Surg 2006
Aug;30(8):1592-604.
(19) van den Berg MG, Rasmussen-Conrad EL, Wei KH, Lintz-Luidens H, Kaanders JH,
Merkx MA. Comparison of the effect of individual dietary counselling and of standard
nutritional care on weight loss in patients with head and neck cancer undergoing
radiotherapy. Br J Nutr 2010 May 5;1-6.
(20) Isenring EA, Capra S, Bauer JD. Nutrition intervention is beneficial in oncology
outpatients receiving radiotherapy to the gastrointestinal or head and neck area. Br J
Cancer 2004 Aug 2;91(3):447-52.
(21) Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Dietary counseling improves
patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients
undergoing radiotherapy. J Clin Oncol 2005 Mar 1;23(7):1431-8.
(22) Ravasco P, Monteiro-Grillo I, Marques VP, Camilo ME. Impact of nutrition on
outcome: a prospective randomized controlled trial in patients with head and neck cancer
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(23) Wood K. Audit of nutritional guidelines for head and neck cancer patients
undergoing radiotherapy. J Hum Nutr Diet 2005 Oct;18(5):343-51.
(24) Elia M, van Bokhorst-de van der Schueren MA, Garvey J, Goedhart A, Lundholm K,
Nitenberg G, et al. Enteral (oral or tube administration) nutritional support and
eicosapentaenoic acid in patients with cancer: a systematic review. Int J Oncol 2006
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(25) Potter J, Langhorne P, Roberts M. Routine protein energy supplementation in adults:
systematic review. Bmj 1998;317(7157):495-501.
(26) Akner G, Cederholm T. Treatment of protein-energy malnutrition in chronic
nonmalignant disorders. Am J Clin Nutr 2001;74(1):6-24.
(27) Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy supplementation in
elderly people at risk from malnutrition (Review). Cochrane Database Syst Rev
2009;(2):CD003288.
(28) Baldwin C, Parsons TJ. Dietary advice and nutritional supplements in the
management of illness-related malnutrition: systematic review. Clin Nutr 2004
Dec;23(6):1267-79.
(29) Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Dietary counseling improves
patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients
undergoing radiotherapy. J Clin Oncol 2005 Mar 1;23(7):1431-8.
(30) Rufenacht U, Ruhlin M, Wegmann M, Imoberdorf R, Ballmer PE. Nutritional
counseling improves quality of life and nutrient intake in hospitalized undernourished
patients. Nutrition 2010 Jan;26(1):53-60.
(31) Wilson MM, Purushothaman R, Morley JE. Effect of liquid dietary supplements on
energy intake in the elderly. Am J Clin Nutr 2002 May;75(5):944-7.

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