Contents
Chapter 1 General introduction 9-18
Chapter 2 Study design: effectiveness and cost-effectiveness of
post-discharge nutritional support in malnourished
elderly patients in comparison with usual care
19-34
Chapter 3 Post-discharge nutritional support in malnourished
elderly patients decreases functional limitations
35-48
Chapter 4 Post-discharge nutritional support in malnourished
elderly patients decreases functional limitations with
no extra costs
49-68
Chapter 5 Short-term oral nutritional intervention with protein
and vitamin D decreases falls in malnourished elderly
patients
69-86
Chapter 6 Effects of nutritional intervention on immune markers
in malnourished elderly
87-106
Chapter 7 Resting energy expenditure in malnourished elderly
patients at hospital admission and three months after
discharge: predictive equations versus measurements
107-128
Chapter 8 Should we feed malnourished cognitively impaired
hospitalized elderly patients?
129-142
Chapter 9 General discussion 143-156
Summary 157-160
Samenvatting 161-164
Dankwoord 165-170
About the author 171-172
Publications 173-176
10
General introduction
Our population is aging, and the number of Europeans aged between 65-79 years is
expected to increase approximately 35% between 2010 and 2030(1). With the
probability, the number of malnourished elderly people will increase proportionally.
Aging comes with an increase in health challenges. As elderly people are vulnerable to
malnutrition, they often have several co-morbidities that are chronic and progressive.
However, malnutrition is not always caused by a disease, it also leads to vulnerability to
illness.
According to the literature, malnutrition is estimated to occur in 25-61% of all elderly
patients suffering from various diseases(2;3).
We expect that a post-discharge nutritional intervention in malnourished elderly
patients will be beneficial for their health and may result in lower health care costs.
Figure 1 presents a simplified overview of relations depicted in this thesis.
General introduction
11
Causes of malnutrition
The World Health Organization (WHO) defines malnutrition as "the cellular imbalance
between supply of nutrients and energy and the body's demand for them to ensure
growth, maintenance, and specific functions”.
Previous studies have identified several determinants for malnutrition in elderly
individuals, such as disease(4-8), older age(5;9), depression(9-11), cognitive
impairment(10), impaired physical functioning(4;10;12;13), dementia(12), toughness in
biting and chewing(10;12), vision problems(7), poor appetite(7;10) and stress(7). Some of
these causes of malnutrition are irreversible. However, others, e.g. physical functioning,
could be improved by accurate nutritional interventions.
Malnutrition also increases ones vulnerability to illness due to the combination of
disease and malnutrition. The metabolism weakens and give rise to a vicious circle of
infection and undernourishment.
Consequences of malnutrition in elderly
Disease-related malnutrition is associated with adverse effects on clinical outcomes, as
has been shown in a large number of studies. These in-hospital adverse effects vary,
from impaired wound healing and postoperative complications, to mortality(14). Poor
nutritional status has not only been associated with in-hospital adverse effects, but also
with adverse effects both pre-admission and post-discharge. As a result of these effects
it appears that there is an increased need for re-hospitalization, a higher general
practitioner consultation rate, higher medication prescription rate, longer rehabilitation,
an increased need for nursing home admission, increased likelihood of requiring home
health care following discharge, early institutionalization and significantly higher total
mortality (15;16).
Post-discharge nutritional intervention
Due to the short hospitalization period followed by rehabilitation at home, it is not very
likely that patients’ nutritional status would improve sufficiently during this short period
of hospital stay. Therefore, the presence of disease-related malnutrition is increasingly
shifting to the post-discharge setting. However, no systematic post-discharge nutritional
support is organized in primary health care in The Netherlands.
Treatment of malnutrition in elderly
To date, randomized controlled trials have shown that additional oral nutritional
supplements can be effective in improving nutritional status in malnourished elderly
people, both in the clinical setting and in the community(17;18). In malnourished
hospitalized patients, oral nutritional supplements has demonstrated improved body
Chapter 1
12
weight and attenuated weight loss, to shorten hospital stay and to improve functional
status(19). In the community, oral nutritional supplements has been shown to increase
activities of daily living, reduce the number of falls and reduce health care
utilization(16;20-22).
Oral nutritional supplements has proven to be effective in increasing body weight(22).
However, there is limited evidence of effectiveness of post-discharge oral nutritional
supplements in malnourished elderly on functional outcomes, like physical
performance, physical activities and functional limitations.
Fall incidents
Fall incidents are a common and serious cause of morbidity and mortality in elderly
people. Fractures resulting from fall incidents, lead to significant healthcare costs(23).
Each year, one in three community-dwelling persons aged 65 years or older, experiences
at least one fall incident(24-26). Loss of muscle mass and strength are regarded as
important risk factors for falls, functional decline and disability(27).
Malnutrition can decrease muscle mass(28) and both vitamin D deficiency and
malnutrition can decrease muscle strength(28;29). In well-nourished community living
elderly people at risk of vitamin D deficiency, vitamin D supplementation has shown to
improve muscle strength, function, and body balance in a dose-related pattern(30).
These benefits include a reduction of fall incidents as shown in epidemiological studies
and randomized clinical trials. Several meta-analyses in healthy people support the
beneficial effects of vitamin D supplementation on falls (31;32).
Malnutrition is also associated with an increased incidence of falls(33;34), however,
studies are insufficient in demonstrating the effects of nutritional intervention in the
prevention of fall incidents.
Immune markers
Both malnutrition and advanced age are known to negatively impact the immune
system. Malnutrition per se affects nearly all aspects of the immune defence system, but
especially impairs cell mediated immunity and resistance to infection(35).
In the elderly, many alterations of both innate and acquired immunity have been
described.
Although the emphasis of most research on immunosenescence has been on T cells,
there is an increasing realization that the subtle changes seen in parameters of innate
immunity, including the acquisition of some characteristics of innate immunity by T cells
themselves(39-41), may have more influence on immunity than so far assumed.
Adequate nutrition is believed to play a role in the maintenance and restoration of
impaired immune-competence, even in old age(42;43). Not only an adequate intake of
General introduction
13
energy and protein play an important role. Also, the correction of certain nutritional
deficiencies has been demonstrated to improve the host’s immunity, which warrants a
place for these nutrients in an adequate diet. However, the optimal intake for a variety of
micronutrients, to improve host’s immunity, has not been established.
To obtain an idea of the possible changes in the immune system in the period
recovering from disease and malnutrition, a broad range of (surrogate) immune markers
(interleukins, complement, C-reactive protein, albumin, TNF-α), endocrine markers
(growth factors), and micronutrients (iron, ferritin, vitamins) will be assessed, to explore
if these different compartments may explain the enhanced recovery of a malnourished
ill elderly population following nutritional intervention.
Costs
Health care policy makers need to make informed decisions about whether to fund new
health care interventions above or in addition to existing ones. To do this they need
information on both the costs and the effects of the alternative treatments, which is
provided by cost-effectiveness studies. In a cost-effectiveness study, the costs and
consequences of two or more different health care interventions are compared(44).
Studies on cost-effectiveness of nutritional interventions in clinical settings are minimal.
In a retrospective cost-analysis of nine randomized controlled trials on nutritional
support, the cost savings aggregated between € 500 and € 12000 per patient in surgical,
orthopaedic, elderly and stroke patients(17). Cost-effectiveness studies of oral nutritional
supplements in the community are lacking.
Energy requirements
Malnutrition is often reversible and can be treated by a dietitian, general practitioner or
medical specialist. To establish optimal goals for dietary intake, it is important to predict
resting energy expenditure. This requires knowledge of individual energy requirements
and relies on accurate methods of assessment. Energy expenditure can be measured by
indirect calorimetry and provides an indication of patients’ energy requirements(45).
This method is not very feasible in most clinical settings, due to time consuming
measurements, lack of trained personnel and expensive equipment. In clinical practice,
predictive equations to determine resting energy expenditure in malnourished, ill and
elderly patients are used as an alternative.
Resting energy expenditure predictive equations have generally been developed in
healthy populations or in critically ill patients. Specific equations for predicting resting
energy expenditure in malnourished hospitalized elderly patients are lacking.
Chapter 1
14
Cognitive impairment
Malnutrition is associated with dementia and often even a precursor in dementia(46-48).
Oral nutritional intake is often inadequate due to impaired ability to complete motor
and perceptual tasks, required for eating and drinking and often prevent the older adult
from accepting help with feeding from caregivers(49;50).
Mortality rates in patients with dementia (≥ 60 years of age) are more than three times
higher in the first year after diagnosis compared to those without dementia(50;51).
Elderly patients, who are not terminally ill and not cognitively impaired, suffering from
malnutrition may benefit from standard nutritional therapy if the life expectancy would
exceed three months(22;52). Keeping in mind the increased mortality rates of
cognitively impaired patients, the question whether or not to start intensive nutritional
therapy for a longer period of time in these patients remains yet to be answered.
Outline of the thesis
Only a limited number of studies have been published on the effects of post-discharge
nutritional support in malnourished elderly individuals and the results were found to be
less impressive or even absent compared to studies on hospitalized patients. Besides,
randomized controlled trials in this setting are scarce. In view of these considerations,
studies on post-discharge nutritional support in malnourished elderly individuals are
imperative. Therefore, this thesis discusses the effectiveness and cost-effectiveness of
post-discharge nutritional support in malnourished elderly patients, starting at hospital
admission up until three months following discharge.
In Chapter 2 the design of this randomized controlled trial is described.
In Chapter 3 the effect of post-discharge nutritional support on the primary outcome,
changes in activities of daily living, are evaluated. Secondary outcomes are changes in
body weight, body composition, and muscle strength.
In Chapter 4 the cost-effectiveness of post-discharge nutritional support in
malnourished elderly patients, from hospital admission up until three months following
discharge, on quality adjusted life years, physical activities and functional limitations is
reported.
In Chapter 5 the effect of the nutritional intervention on falls is presented.
In Chapter 6 the effect of nutritional intervention on immune markers, endocrine
markers and micronutrients is described.
In Chapter 7 resting energy expenditure predictive equations are compared with
measured values at hospital admission and again three months following discharge.
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