Content uploaded by Javier Alonso Renedo
Author content
All content in this area was uploaded by Javier Alonso Renedo on Dec 25, 2019
Content may be subject to copyright.
Effect of Exercise Intervention on Functional Decline
in Very Elderly Patients During Acute Hospitalization
A Randomized Clinical Trial
Nicolás Martínez-Velilla,PhD, MD; Alvaro Casas-Herrero, PhD, MD; Fabricio Zambom-Ferraresi, PhD;
Mikel López Sáez de Asteasu, MSc; Alejandro Lucia, PhD, MD; ArkaitzGalbe te,PhD; Agurne García-Baztán, MD;
Javier Alonso-Renedo, MD; Belen González-Glaría, PhD,MD; María Gonzalo-Lázaro, MD; Itziar Apezteguía Iráizoz, PhD, MD;
Marta Gutiérrez-Valencia,PharmD; Leocadio Rodríguez-Mañas, PhD, MD; Mikel Izquierdo, PhD
IMPORTANCE Functional decline is prevalent among acutely hospitalized older patients.
Exercise and early rehabilitation protocols applied during acute hospitalization can prevent
functional and cognitive decline in older patients.
OBJECTIVE To assess the effects of an innovative multicomponent exercise intervention on
the functional status of this patient population.
DESIGN, SETTING, AND PARTICIPANTS A single-center, single-blind randomized clinical trial
was conducted from February 1, 2015, to August 30, 2017, in an acute care unit in a tertiary
public hospital in Navarra, Spain. A total of 370 very elderly patients undergoing acute-care
hospitalization were randomly assigned to an exercise or control (usual-care) intervention.
Intention-to-treat analysis was conducted.
INTERVENTIONS The control group received usual-care hospital care, which included physical
rehabilitation when needed. The in-hospital intervention included individualized
moderate-intensity resistance, balance, and walking exercises (2 daily sessions).
MAIN OUTCOMES AND MEASURES The primary end point was change in functional capacity
from baseline to hospital discharge, assessed with the Barthel Index of independence and the
Short Physical Performance Battery (SPPB). Secondary end points were changes in cognitive
and mood status, quality of life, handgrip strength, incident delirium, length of stay, falls,
transfer after discharge, and readmission rate and mortality at 3 months after discharge.
RESULTS Of the 370 patients included in the analyses, 209 were women (56.5%); mean (SD)
age was 87.3 (4.9) years. The median length of hospital stay was 8 days in both groups
(interquartile range, 4 and 4 days, respectively). Median duration of the intervention was
5 days (interquartile range, 0); there was a mean (SD) of 5 (1) morning and 4 (1) evening
sessions per patient. No adverse effects were observed with the intervention. The exercise
intervention program provided significant benefits over usual care. At discharge, the exercise
group showed a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the SPPB scale and
6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index over the usual-care group.
Hospitalization led to an impairment in functional capacity (mean change from baseline to
discharge in the Barthel Index of −5.0 points (95% CI, −6.8 to −3.2 points) in the usual-care
group, whereas the exercise intervention reversed this trend (1.9 points; 95% CI, 0.2-3.7
points). The intervention also improved the SPPB score (2.4 points; 95% CI, 2.1-2.7 points) vs
0.2 points; 95% CI, −0.1 to 0.5 points in controls). Significant intervention benefits were also
found at the cognitive level of 1.8 points (95% CI, 1.3-2.3 points) over the usual-care group.
CONCLUSIONS AND RELEVANCE The exercise intervention proved to be safe and effective to
reverse the functional decline associated with acute hospitalization in very elderly patients.
TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02300896
JAMA Intern Med. doi:10.1001/jamainternmed.2018.4869
Published online November 12, 2018.
Invited Commentary
Author Audio Interview
Video and Supplemental
content
Author Affiliations: Author
affiliations are listed at the end of this
article.
Corresponding Author: Mikel
Izquierdo, PhD, Department of
Health Sciences, Public University of
Navarra, Av. De Barañain s/n 31008
Pamplona, Navarra, Spain
(mikel.izquierdo@gmail.com).
Research
JAMA Internal Medicine | Original Investigation
(Reprinted) E1
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
The provision of inpatient acute care for frail older adults
who are at risk of adverse outcomes is becoming a
major clinical issue in our aging societies.
1-4
In this
regard, acute hospital admissions are a major contributor to
disability in the elderly.
5
Despite resolution of the reason for
hospitalization, patients, especially those who are frail, are
often discharged with a new major disability.
6
More than half
of all older adults do not recover to their preadmission func-
tional levels 1 year after discharge, with high rates of nursing
home placement and death.
7-9
This is a problem that health
care professionals and policy makers should prioritize given
the expectations of further growth of the population seg-
ment composed of elderly people.
Acute hospitalized older patients, including those who are
able to walk independently, spend most of their hospital time
in bed.
9,10
In addition to deteriorating their functional status,
bed rest increases the risk for cognitive decline and dementia
in the elderly.
11
The epidemic of low mobility during hospital-
ization is caused by several factors, including a failure to
apply efficient models for management of older patients,
12,13
the notion that reducing mobility will prevent falls, the cul-
ture of bed rest, or hospital design.
14
Exercise and early rehabilitation protocols applied during
acute hospitalization can prevent functional and cognitive de-
cline in older patients and are associated with a reduced length
of stay and lower costs.
15
Yet,patients with cognitive impairment
or multimorbidity at baseline are commonly excluded from
exercise intervention trials, and only conservativeor traditional
programs (ie, focusing on light walking while avoidingresistance
training) have been typically applied to elders who are acutely
hospitalized.
14,16
The benefits of a multicomponent exercise
intervention consisting of resistance (power),balance, and gait-
retraining exercises to attenuate functional decline in frail
nonagenarians in long-term care have been shown.
17
To the best
of our knowledge, this type of intervention has not been imple-
mented in acutely hospitalized patients of advanced age(includ-
ing octogenarians and nonagenarians).
The present study is in line with the long trajectory of
research that has explored the possibilities of modifying tra-
ditional models of hospitalization in Acute Care of Elderly (ACE)
units
8,18
but goes a step further by adding the individualized
and adapted prescription of multicomponent exercise to
each patient. The main purpose of our study was therefore to
assess the effects of a multicomponent exercise intervention
performed by older adults during acute hospitalization for
functional, cognition, and well-being status. Other out-
comes, such as length of stay or falls, were also assessed.
Methods
Design
The study was a randomized clinical trial (RCT) performed ac-
cording to the SPIRIT 2013 and the CONSORT statement for
transparent reporting.
19,20
The protocol is available in
Supplement 1. The RCT was conducted from February 1, 2015,
to August 30, 2017, in the ACE unit of the department of
geriatrics in a tertiary public hospital (Complejo Hospitalario
de Navarra, Pamplona, Spain). This department has 35 beds
allocated to the unit and its staff is composed of 8 geriatricians
(distributed in the ACE unit, orthogeriatrics, and outpatient
consultations). Admissions in the ACE unit are mainly from the
accident and emergency department, with heart failure and
infectious diseases being the main causes of admissions (eTable
in Supplement 2). When the disability generated by the patho-
logic factors that caused admission in the ACE unit requires
long-term care, patients are usually referred to another,
medium-stay hospital.
The study followed the principles of the Declaration of
Helsinki
21
and was approved by the Complejo Hospitalario
de Navarra Clinical Research Ethics Committee. All patients
or their legal representatives provided written informed con-
sent. There was no financial compensation.
Acutely hospitalized patients who met inclusion criteria
were randomly assigned to the intervention or control (usual-
care) group within the first 48 hours of admission. Usual care
is offered to the patient by the geriatricians of our depart-
ment and consists of standard physiotherapy focused on
walking exercises for restoring the functionality conditioned
by potentially reversible abnormalities. A formal exercise
prescription was not provided at study entry and patients were
instructed to continue with the current activity practices
through the duration of the study.
Participants and Randomization
All of the patients admitted to the ACE unit were evaluated by
geriatricians. We focused on a particularly vulnerable popula-
tion segment, but at the same time with a level of functional
reserve and cognitive capacity high enough to allow them to
perform the programmed exercise intervention. Thus, a trained
research assistant (N.M.-V., A.C.-H., A.G.-B., J.A.-R., B.G.-G.,
M.G.-L., or I.A.I.) conducted a screening interview to deter-
mine whether potentially eligible patients met the following
inclusion criteria: age 75 years or older, Barthel Index score of
60 or more (scale, 0 [severe functional dependence] to 100
[functional independence]),
22
being able to ambulate (with/
without assistance), and being able to communicate and
collaborate with the research team. Exclusion criteria in-
cluded expected length of stay less than 6 days, very severecog-
nitive decline (ie, Global Deterioration Scale score, 7),
23
termi-
nal illness, uncontrolled arrhythmias, acute pulmonary
Key Points
Question Can the functional and cognitive impairment associated
with the acute hospitalization of older adults be reversed?
Findings Thisrandomizedclinicaltrial including370 hospitalizedelderly
patients shows that the prescribed exercise intervention provided
significant benefitsover usualcare.At discharge,significant differences
between the exercise intervention and the control groups were noted
forfunctionalindependence aswellas cognitiveand quality oflife level.
Meaning An individualized, multicomponent exercise program
proved safe and effective to reverse the functional decline
associated with acute hospitalization in very elderly patients.
Research Original Investigation Effect of Exercise Intervention on Functional Decline in Very Elderly Patients
E2 JAMA Internal Medicine Published online November 12, 2018 (Reprinted) jamainternalmedicine.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
embolism, recent myocardial infarction, recent major surgery,
or extremity bone fracture in the past 3 months.
After the baseline assessment was performed, partici-
pants were randomly assigned following a 1:1 ratio, without
restrictions.
24
The assessment staff were blinded to the main
study design and group allocation. Participants were explic-
itly informed and reminded not to discuss their randomiza-
tion assignment with the assessment staff.
The costs derived from the intervention werebasic ally those
generated by hiring 1 physiotherapist(M.L.S.deA.) ad hoc for the
project and the collaboration of a researcher (with a PhD back-
ground in exercise physiology) (F.Z.-F.) who shared the work
during 7 days a week for the duration of the study. An initial
investment of €4000 (US $4645) was made to buy the weight-
training equipment (ie, €3500 [US $4064] for the sum of 1 leg
press, 1 bilateral knee extension, and 1 seated bench [chest]
press machine) (Video 1) and approximately €500 (US $580) for
dumbbells, ankle weights, and handgrip balls (Video 2).
Intervention
The usual-care group received habitual hospital care, which in-
cluded physical rehabilitation when needed. The intervention
was programmed in 2 daily sessions (morning and evening) of
20 minutes’ duration during 5 to 7 consecutive days (including
weekends). An experienced fitnessspec ialist with in-depth train-
ing on safe patient handling techniques(F.Z.-F.) supervised each
patient’s session and provided instructions and encourage-
ment. Adherence to the exercise intervention program was
documented in a daily register. A session was considered com-
pleted when 90% or more of the programmed exercises were
successfully performed.
25
Participants and their family mem-
bers were familiarized with the training procedures before the
start of the intervention.
Each session was performed in a room equipped ad hoc in
the geriatric ACE unit. Exercises were adapted from the multi-
component physical exercise program Vivifrail to preventweak-
ness and falls.
26
The morning sessions included individual-
ized supervised progressive resistance, balance, and walking
training exercises. The resistance exercises weretailored to the
individual’s functional capacity using variable resistance train-
ing machines (Matrix; Johnson Health Techand Exercycle S.L.,
BH Group) aiming at 2 to 3 sets of 8 to 10 repetitions with a load
equivalent to 30% to 60% of the 1-repetition maximum.
25
Par-
ticipants performed 3 exercises involving mainly lower-limb
muscles (squats rising from a chair,leg press, and bilateral knee
extension) and 1 involving the upper-body musculature (seated
bench [chest] press) (Video 1). They were instructed to per-
form the exercises at a high speed to optimize muscle powerout-
put, and care was taken to ensure proper exercise execution.
Balance and gait retraining exercises gradually progressed
in difficulty and included the following: semi-tandem foot
standing, line walking, stepping practice, walking with small
obstacles, proprioceptive exercises on unstable surfaces (foam
pads sequence), altering the base of support, and weight trans-
fer from 1 leg to the other (Video 3). The evening session con-
sisted of functional unsupervised exercises using light loads (ie,
0.5- to 1-kg anklets and handgrip ball), such as knee extension
and flexion, hip abduction, and daily walking in the corridor of
the acute care unit with a duration based on the clinical physi-
cal exercise guide Vivifrail
26
(Video 2).
18
Participants in the
videos were filmed at discharge.
As soon as the clinician in charge of the patient consid-
ered that their hemodynamic situation was acceptable and the
patient could collaborate, the following end points were
assessed and the intervention was started. End points werealso
assessed on the day of discharge.
End Points
The primary end point was change in functional capacity from
baseline (beginning of the intervention) to hospital discharge,
as assessed with the Short Physical Performance Battery (SPPB),
which combines balance, gait velocity, and leg strength as a
single score on a 0 (worst) to 12 (best scale),
27
and the Barthel
Index of independence during activities of daily living (ADLs)
from 2 weeks prior to admission to hospital discharge. The mag-
nitude of meaningful change (ie, clinically significant) was 1
point for the SPPB
28
and 5 points for the Barthel Index.
29,30
Secondary end points included changes in cognitive capac-
ity as assessed with the Mini-Mental State Examination
(30-point questionnaire; scale of 0 [worst] to 30 [best]),
31
mood
status (15-item Yesavage Geriatric Depression Scale; Spanish
version; scale of 0 [best] to 15 [worst]),
23
visual analog scale of
the EuroQol–5 Dimension (EQ-5D) questionnaire for quality
of life (QoL) assessment (Spanish version of the EQ-5D
32
; scale
of 0 [worst health state imaginable] to 100 [best health state
imaginable]), and handgrip strength (dominant hand).
33
Other
secondary end points included development of delirium (as
assessed with the Confusion Assessment Method; feature 1,
acute onset and fluctuating course; feature 2, inattention;
feature 3, disorganized thinking; and feature 4, altered level of
consciousness, with diagnosis of delirium requiring the pres-
ence of features 1 and 2 and either 3 or 4),
34
length of hospital
stay, falls during hospitalization, transfer after discharge, and
readmission rate and mortality at 3 months after discharge.
Statistical Analysis
We used the intention-to-treat approach. Between-group com-
parisons of continuous variables were conducted using linear
mixed models. Time was treated as a categorical variable. The
models included group, time, and group by time interaction
as fixed effects, and participants as random effect. For each
group, data are expressed as change from baseline (admis-
sion) to discharge, determined by the time coefficients (95%
CI) of the model. The primary conclusions about effective-
ness of exercise intervention were based on between-group
comparisons of change in functional capacity from baseline
(beginning of the intervention) to hospital discharge, as
assessed with the SPPB and the Barthel Index of indepen-
dence during ADLs and determined by the time by group in-
teraction coefficients of the model.
Comparisons of secondary end points indicative of ad-
verse events or hospitalization wereperformed with the Mann-
Whitney test for nonnormally distributed quantitative data,
mid–Pvalue exact test for rates, and χ
2
or Fisher tests for cat-
egorical data. Using the χ
2
test for linear trend, we also com-
pared the proportion of patients in each group showing an
Effect of Exercise Intervention on Functional Decline in Very Elderly Patients Original Investigation Research
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online November 12, 2018 E3
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
improvement, no change, or worsening at discharge com-
pared with baseline on the SPPB scale and Barthel Index.
All comparisons were 2-sided, with a significance level
of .05, except for the analysis of the primary outcome
(change in functional capacity as assessed with the SPPB
scale and Barthel Index), where the Bonferroni-Holm
multiple test adjustment was applied. All statistical analy-
ses were made with SPSS, version 20 (IBM Corp) and R,
version 3.2.2 (R Foundation) software.
Results
The study flow diagram is shown in Figure 1. No significant dif-
ferences were found between groups at baseline for demo-
graphic and medical characteristics or for study end points
(Table 1). Of the 370 patients included in the analyses, 209 were
women (56.5%); mean age was 87.3 (4.9) years (range, 75-101
years, with 130 patients [35.1%]being nonagenarians). The me-
dian length of hospital stay was 8 days in both groups (inter-
quartile range [IQR], 4 and 4 days, respectively).The mean (SD)
number of intervention days for each patientwas 5.3 (0.5) days
(IQR, 0 days), with most training days (97%) being consecu-
tive. The mean number of completed morning and eveningses-
sions per patient was 5 (1) and 4 (1), respectively. Adherence
to the intervention was 95.8% for the morningsessions (ie, 806
successfully completed sessions of 841 total possible ses-
sions) and 83.4% in the evening sessions (574 of 688 success-
fully completed sessions). No adverse effects associated with
the prescribed exercises were recorded and no patient had to
interrupt the intervention or had their hospital stay modified
because of it.
The primary analyses showed that the exercise interven-
tion program provided a significant benefit over usual care. At
discharge (ie, at the primary time point), the exercise group
showed a mean increase of 2.2 points (95% CI, 1.7 to 2.6points)
on the SPPB scale and 6.9 points (95% CI, 4.4 to 9.5 points) on
the Barthel Index over the usual-care group (Table 2). Patients
Figure 1. Study Flow Diagram
421 Assessed for eligibility
51 Excluded
35 Declined to participate
16 Did not meet inclusion
criteria
370 Randomized
28 Discontinued the study
5Did not give consent
5Transferred to another
department
2Died during hospitalization
10 Early discharge
6Clinical worsening
32 Discontinued the study
9Did not give consent
1Transferred to another
department
2Died during hospitalization
5Early discharge
15 Clinical worsening
185 Randomized to control
group (usual care)
185 Randomized to intervention
group
185 Analyzed185 Analyzed
Progress through the phases of the parallel randomized trial of the groups.
Table 1. Main Demographic, Clinical, Functional, and End Point Data
at Baseline by Group
a
Variable
Mean (SD)
Control Group
(n = 185)
Intervention Group
(n = 185)
Demographic data
Age, y 87.1 (5.2) 87.6 (4.6)
Women, No. (%) 109 (58.9) 100 (54.1)
BMI 26.9 (4.9) 27.1 (4.4)
Clinical data
No. of diseases
b
9 (6) 9 (6)
CIRS, median (IQR), score
c
12 (5) 13 (5)
Zarit Caregiver Burden Interview,
median (IQR), score
d
41 (14) 44 (13)
MNA, median (IQR), score
e
24 (4) 24 (4)
6-m Gait velocity test, s 16.1 (8.8) 16.2 (13.1)
1RM leg press, kg 62 (31) 57 (25)
1RM chest press, kg 25 (12) 24 (11)
1RM knee extension, kg 41 (14) 39 (13)
Primary end point measures
SPPB scale
f
4.7 (2.7) 4.4 (2.5)
Barthel Index
g
83 (17) 84 (17)
Secondary end point measures
Mini-Mental State Examination
h
23 (4) 22 (5)
Yesavage Geriatric
Depression Scale
i
3.6 (2.9) 4.0 (2.4)
Quality of life
j
60 (21) 58 (22)
Delirium, %
k
12 17
Handgrip, kg 17 (8) 17 (6)
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided
by height in meters squared); CIRS, Cumulative Illness Rating Scale;
IQR, interquartile range; MNA, Mini-Nutritional Assessment; 1RM, 1 repetition
maximum; SPPB, Short Physical Performance Battery.
a
No statistically significant differences were found between groups (all P> .10).
b
The most prevalent diseases were hypertension, heart failure, dyslipidemia,
osteoarthritis, cardiac arrhythmias, chronic obstructive pulmonary disease,
chronic gastritis/gastroesophageal reflux, chronic kidney disease, and urinary
incontinence.
c
The CIRS scale evaluates individual body systems, ranging from 0 (best)
to 56 (worst).
d
The Zarit Caregiver Burden Interview ranges from little or no burden
(0-21 points), mild to moderate burden (21-40 points), moderate to severe
burden (41-60 points), to severe burden (61-88 points).
e
The Mini-Nutritional Assessment ranges from normal nutritional status
(24-30 points), risk of malnutrition (17-23.5 points), or malnourished (<17
points).
f
The SPPB scale ranges from 0 (worst) to 12 (best).
g
The Barthel Index ranges from 0 (severe functional dependence) to 100
(functional independence).
h
The Mini-Mental State Examination ranges from 0 (worst) to 30 (best).
i
The YesavageGeriatric Depression Scale ranges from 0 (best) to 15 (worst).
j
Measured using the visual analog scale of the EuroQol Questionnaire–5
Dimensions, with the score ranging from 0 (worst health state imaginable)
to 100 (best health state imaginable).
k
Measured using the Confusion Assessment Method, with feature 1 indicating
acute onset and fluctuating course; feature 2, inattention; feature 3, disorganized
thinking; and feature 4, altered level of consciousness, with diagnosis of delirium
requiring the presence of features 1 and 2 and either 3 or 4).
Research Original Investigation Effect of Exercise Intervention on Functional Decline in Very Elderly Patients
E4 JAMAInternal Medicine Published online November 12, 2018 (Reprinted) jamainternalmedicine.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
in the intervention group showed improvements at discharge
compared with baseline in functional and cognition status in-
dicators, depression, QoL, and handgrip, whereas no such trend
was found in the control group (Table 2). Acute hospitalization
per se led to significant impairment in patients’ functional
ability during ADLs (ie, mean change from baseline to dis-
charge on the Barthel Index of −5.0 points (95%CI, −6.8 to −3.2
points) in the control group, whereas the exercise intervention
reversed this trend (1.9 points; 95% CI, 0.2 to 3.7 points).
Furthermore, the percentage distribution of patients with im-
provements, no changes, or worsening on the SPPB scale or
Barthel Index from admission to discharge significantly dif-
fered between the 2 groups, indicating a beneficial interven-
tion effect for both assessments (37.9% vs 85.3% [SPPB] and
9.2% vs 36.3% [Barthel index]; both P< .001 for the control and
intervention groups, respectively) (Figure 2).
We found significant differences between groups in all the
secondary end points indicative of cognitive status (Mini-
Mental State Examination), depression (Geriatric Depression
Scale), and QoL (visual analog scale of the EQ-5D), as well as
in handgrip (all P≤ .001) (Table 2). There were, however,no sig-
nificant differences between groups in the remainder of sec-
ondary outcomes, including incident delirium (P> .10) (Table 2),
length of hospitalization, proportion of patientshaving 1 or more
falls during hospitalization, 3-month hospital readmission
rate/mortality, or patient transfer (all P>.10)(Table 3).
Discussion
Our study shows that an individualized, multicomponent ex-
ercise intervention including low-intensity resistance training
exercises performed during a short period (mean, 5 days) pro-
vides a significant benefit over usual care and can help to
reverse the functional decline associated with acute hospital-
ization in older adults. Acute hospitalization per se led to im-
pairment in patients’ functional ability during ADLs, whereas
the exercise intervention reversed this trend. We also ob-
served an increase in the SPPB score and handgrip strength
after the intervention, with the opposite response found in the
control group. We believe that this finding is also important be-
cause there is meta-analytic evidence that functional capacity
and both muscle strength, as assessed by SPPB and handgrip
strength, and muscle mass tend to decrease in the elderly dur-
ing hospitalization (at least in electively admitted patients),
35
with muscle strength and mass being associated with disabil-
ity, morbidity, and cardiometabolic disease–related mortality.
36
Acute hospital admissions play an important role in the dis-
abling process at the elderly years, owing to the deleterious ef-
fects of the presenting illness or injury and the hazards of hos-
pital stay.
5
Regarding the latter, nosocomial disability is usually
linked to poor mobility, with the most active patients showing
lesser functional impairment than their less-active peers.
37
Thus,
preservation of functional capacity, mobility, and mental ca-
pacities should be the focus of the clinical management of the
elderly population with disease,
2,38
including also during acute
hospitalization phases. However, a recent RCT showed no sig-
nificant benefit of a simple in-hospital mobility program con-
sisting of ambulation up to twice daily and a behavioral strat-
egy to encourage mobility in older (mean age, 74years) patients’
ability to perform ADLs after acute hospitalization (median
length of stay, 3 days).
16
Thus, our data, together with those of
previous research, suggest that interventions beyond walking
stimulation are needed to preserve functional capacity in older
patients during acute hospitalization.
Few RCTs have evaluated the effects of exercise interven-
tion on functional outcomes in acutely hospitalized older adults.
Although in-hospital exercise interventions are virtually free of
adverse events and may reduce lengthof stay or hospital costs,
meta-analytic evidence is lacking to support the benefits of such
interventions in the functional capacity of acutely ill elderly
patients.
15
In this respect, our results indicate that, despite its
short duration, a multicomponent exercise approach is effec-
tive in improving the functional status (measured by SPPB scale,
Table 2. Results of Primary and Secondary End Points by Group
a
Variable
b
Control
Group
Intervention
Group
Between-Group
Difference (95% CI)
PValue
Between
Groups
Primary End Point: Change in Functional Capacity
SPPB scale (balance, gait ability, leg strength) 0.2 (−0.1 to 0.5) 2.4 (2.1 to 2.7) 2.2 (1.7 to 2.6) <.001
Barthel Index (ADLs) −5.0 (−6.8 to −3.2) 1.9 (0.2 to 3.7) 6.9 (4.4 to 9.5) <.001
Secondary End Points
Cognitive status
MMSE 0.3 (−0.1 to 0.6) 2.1 (1.7 to 2.5) 1.8 (1.3 to 2.3) <.001
Depression (GDS) 0.7 (0.4 to 0.9) −1.3 (−1.7 to −1.1) −2.0 (−2.5 to −1.6) <.001
QoL (EuroQol-5D) −2.2 (−5.8 to 1.3) 11.0 (7.5 to 14.5) 13.2 (8.2 to 18.2) <.001
Incident delirium (CAM), % 8.3 14.6 OR, 1.9 (0.9 to 4.0) .12
Handgrip strength, kg −0.8 (−1.2 to −0.5) 1.5 (1.1 to 1.8) 2.3 (1.8 to 2.8) <.001
Abbreviations: ADLs, activities of daily living; CAM, Confusion Assessment
Method; EurolQol-5D, EuroQol Questionnaire–5 Dimensions; GDS,Yesavage
Geriatric Depression Scale; MMSE, Mini-Mental State Examination; OR, odds
ratio; QoL, quality of life; SPPB, Short Physical Performance Battery.
a
All data, except for CAM, were derived from linear mixed-effects model. For
each group, data are expressed as change from baseline (admission) to
discharge, determined by the time coefficients (95% CI) of the model. For
example, for the SPPB scale, 0.2 corresponds to the coefficient estimated
from the model. The between-group difference was determined with
time × group interaction coeff icient. ForCAM, data are the proportion of
patients in whom delirium developed.
b
Explanations of scales used are given in the footnotes to Table1.
Effect of Exercise Intervention on Functional Decline in Very Elderly Patients Original Investigation Research
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online November 12, 2018 E5
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
Barthel Index) of very old adults. These benefits have been rarely
demonstrated in the literature,
39
especially after such a short
period.
37
By contrast, previous trials using early mobilization
with no resistance exercises have proven beneficial in improv-
ing the functional recovery of critically ill younger adults.
40-42
It therefore seems that a more complete, multicomponent ex-
ercise intervention, such as the one described herein, particu-
larly with the addition of resistance training, is needed to coun-
teract the muscle weakness of older hospitalized patients, with
muscle tissue deterioration being a main determinant of func-
tional independence in the elderly years. Although beneficial
effects were obtained in the ability to perform ADLs and physi-
cal performance, the intervention did not change readmission
rate and mortality at 3 months. In effect, in a very old popula-
tion such as ours, with a theoretically short life expectancy af-
ter hospitalization, the objective of our intervention should
be to increase the quality rather than quantity of life. Future fol-
low-up analyses might allow us to determine if our interven-
tion can benefit patients in terms of other important out-
comes, such as readmission rate, hip fracture prevention, or
length of future hospitalizations.
Our results also showed significant intervention benefits
at the cognitive, affective, and QoL levels. Although there is
some disagreement regarding the effects of exercise interven-
tions on the cognitive function of the elderly, it seems that mul-
ticomponent exercise training, such as the one applied in this
RCT, may have the most beneficial results.
43
The interven-
tion was, however, unable to influence the occurrence of
incident delirium, which is in line with previous research.
44
Because delirium is an independent predictor of sustained poor
cognitive and functional status during the year after hospital-
ization in the elderly,
45
future research should explore whether
other in-hospital exercise interventions could perhaps have a
preventive effect on the incidence of delirium.
Limitations
Our study has some limitations. The poor condition of sev-
eral patients precluded assessment of change from baseline to
discharge on the SPPB scale and Barthel Index in 7 (2.3%) and
19 (6.1%), respectively,of the partic ipantswho completed the
intervention. This prevalence limits the generalizability of our
findings to the most debilitated patients. Also,we did not col-
lect functional and cognitive data prior to the acute illness.
However, functional status 2 weeks before admission was in-
directly measured with the Barthel Index score at baseline,
but the risk of bias is likely to increase when retrospective
Figure 2. Discrete Changes From Baseline to Discharge
According to Treatment Group and Within-Group Score Change
Distribution for Both Groups
100
80
90
60
70
40
50
20
10
30
0
Patients, %
Intervention
Group
Control
Group
Change in Barthel index from admission
to discharge
A
Change in Barthel index
C
50
40
30
20
10
0
–50
–40
–30
–20
–10
Score, Points
Control
Group
Intervention
Group
Worse
Unchanged
Better
Much better
Much worse
100
80
90
60
70
40
50
20
10
30
0
Patients, %
Intervention
Group
Control
Group
Change in SPPB from admission to discharge
B
Change in SPPB
D
10
8
6
4
2
0
–10
–8
–6
–4
–2
Score, points
Control
Group
Intervention
Group
Worse
Unchanged
Better
Much better
Much worse
Changes from baseline to discharge (A and B) and within-group punctuation
change distribution (C and D). A, Barthel Index changes: much better indicates an
improvement of more than 10 points, better indicates an improvement of 10 or
less points, unchanged indicates no difference, worse indicates a decline of 10 or
less points, and much worse indicates a decline of more than 10 points.
B, Short Physical Performance Battery (SPPB) scale: much better indicates an
improvement of 3 or more points, better indicates an improvement of 2 points,
slightly better indicates an improvement of 1 point, unchanged indicates no
difference, and worse indicates a decline. Differences between the treatment
groups were tested with the χ
2
test for linear trend and revealed a significant
intervention effect (P< .01) for both the SPPB scale and Barthel Index. The
proportion of patients showing overall improvement and worsening in the Barthel
Index or SPBB scale was significantly higher and lower,respec tively, in the
intervention than in the control group (Pvalue <.001 with χ
2
test). In the box
plots, the box indicates Q1 to Q3; horizontal line within the box, median; error
bars, 1.5 × interquartile range; and solid circles beyond the error bars, outliers.
Table 3. Resultsof Secondar y End PointsIndicative of Adverse Events
or Hospitalization
End Point
Control
(n = 185)
Intervention
(n = 185)
PValue
Between
Groups
Length of hospital stay,
median (IQR), d
8 (4) 8 (4) .25
a
Falls during hospitalization,
No./No. (% per group
experiencing ≥1 fall)
0/139 4/146 (2.7) .12
b
3-mo Hospital readmission
rate (10-person/3-mo),
median (IQR)
2.5 (1.8-3.3) 2.4 (1.7-3.2) .82
c
3-mo Mortality, % 9.7 11.9 .62
d
Transfer, %
Home 91.4 92.4
.55
b
Institutionalization 1.1 2.2
Other 7.6 5.4
Abbreviations: ADL, activities of daily living; IQR, interquartile range.
a
Mann-Whitney test.
b
Fisher exact test.
c
Mid–Pvalue exact test.
d
χ
2
Tes t.
Research Original Investigation Effect of Exercise Intervention on Functional Decline in Very Elderly Patients
E6 JAMAInternal Medicine Published online November 12, 2018 (Reprinted) jamainternalmedicine.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
information is recruited with this subjective self-report scale.
In addition, this was a single RCT; thus, replication is needed
in other cohorts.
Our study, nevertheless, has several strengths, including
its novelty. Most exercise interventions in geriatric patients
have been performed in nonacute settings, that is, at the com-
munity level, in institutionalized elders, or in those hospital-
ized for rehabilitation purposes. Furthermore, older patients
with multiple comorbidities are routinely excluded from
exercise studies owing to acute medical conditions, whereas
the patients had a mean (SD) of 9 (6) comorbidities. We did not
exclude patients with dementia (except for very severe cases,
ie, those with the highest score [7] on the Global Deteriora-
tion Scale) or those who were unable to walk independently.
Besides the very poor health status of our patients compared
with those of previous RCTs evaluating acutely hospitalized
elders, our study is unique in several aspects, such as the
advanced age of the cohort (overall mean, 87.3 years; range,
75-101 years, with 130 patients (35.1%) being nonagenarians),
the large sample size, and the innovative protocol we applied
by adding specific resistance-training machines and with daily
individualized adjustment of loads. To minimize potentialbias,
end point assessment was consistently performed following
a standardized test protocol and the investigators were
unaware of a patient's previous test scores when retesting.
Conclusions
An individualized, multicomponent exercise program
proved to be safe and effective to reverse functional decline
associated with acute hospitalization in very elderly
patients. It also was shown to provide benefit in other end
points, such as cognitive status and QoL. These findings
open the possibility for a shift from the traditional disease-
focused approach in hospital acute care units for elders to
one that recognizes functional status as a clinical vital sign
that can be impaired by traditional (bed rest–based)
hospitalization but effectively reversed with specific
in-hospital exercises.
ARTICLE INFORMATION
Accepted for Publication: July 27, 2018.
Published Online: November 12, 2018.
doi:10.1001/jamainternmed.2018.4869
Author Affiliations: Geriatric Department, Complejo
Hospitalario de Navarra, Pamplona, Navarra,Spain
(Martínez-Velilla,Casas-Herrero, García-Baztán,
Alonso-Renedo, González-Glaría, Gonzalo-Lázaro,
Apezteguía Iráizoz, Gutiérrez-Valencia); Biomedical
Research Centre of the Government of Navarre and
Navarra Institute for Health Research, Pamplona,
Navarra, Spain (Martínez-Velilla, Casas-Herrero,
Zambom-Ferraresi, López Sáez de Asteasu, Galbete,
García-Baztán, Alonso-Renedo, González-Glaría,
Gonzalo-Lázaro,Apezteguía Iráizoz,Gutiérrez-Valencia,
Izquierdo); Biomedical Research Networking Centers
of Frailtyand Healthy Aging, Instituto de Salud Carlos
III, Madrid, Spain (Martínez-Velilla,Casas-Herrero,
Zambom-Ferraresi, López Sáez de Asteasu,
Rodríguez-Mañas, Izquierdo); Department of Health
Sciences, Public University of Navarra, Pamplona,
Navarra, Spain (Martínez-Velilla, Casas-Herrero,
Zambom-Ferraresi, López Sáez de Asteasu,
Gutiérrez-Valencia, Izquierdo); Faculty of Sports
Sciences, Universidad Europea de Madrid, Madrid,
Spain (Lucia); Research Institute of the Hospital 12 de
Octubre (“i+12”), Madrid, Spain (Lucia); Geriatric
Department, HospitalUniversitario deGetafe, Getafe,
Madrid, Spain (Rodríguez-Mañas).
Author Contributions: Drs Martínez-Velillaand
Izquierdo had full access to all of the data in the
study and take responsibility for the integrity of the
data and the accuracy of the data analysis.
Concept and design: Martínez-Velilla, Casas-Herrero,
Zambom-Ferraresi, López Sáez de Asteasu,
Alonso-Renedo, Apezteguía Iráizoz,
Rodríguez-Mañas, Izquierdo.
Acquisition, analysis, or interpretation of data:
Martínez-Velilla,Casas-Herrero, Zambom-Ferraresi,
López Sáez de Asteasu, Lucia, Galbete, García-Baztán,
González-Glaría, Gonzalo-Lázaro, Gutiérrez-Valencia,
Rodríguez-Mañas, Izquierdo.
Drafting of the manuscript: Martínez-Velilla,
Casas-Herrero, Zambom-Ferraresi,Lucia, Galbete,
García-Baztán, Gonzalo-Lázaro, Izquierdo.
Critical revision of the manuscript for important
intellectual content: Martínez-Velilla, Casas-Herrero,
Zambom-Ferraresi, López Sáez de Asteasu, Lucia,
Galbete, Alonso-Renedo, González-Glaría,
Apezteguía Iráizoz, Gutiérrez-Valencia,
Rodríguez-Mañas, Izquierdo.
Statistical analysis: Zambom-Ferraresi, Lucia,
Galbete, Izquierdo.
Obtained funding: Martínez-Velilla, Casas-Herrero,
Zambom-Ferraresi, González-Glaría,
Rodríguez-Mañas, Izquierdo.
Administrative, technical, or material support:
Martínez-Velilla,Casas-Herrero, Zambom-Ferraresi,
González-Glaría, Gutiérrez-Valencia,
Rodríguez-Mañas, Izquierdo.
Supervision: Martínez-Velilla,Casas-Herrero,
Zambom-Ferraresi, López Sáez de Asteasu, Lucia,
Alonso-Renedo, Gonzalo-Lázaro,
Apezteguía Iráizoz, Rodríguez-Mañas, Izquierdo.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was funded by a
Gobierno de Navarra project Resolución grant
2186/2014 and acknowledged with the “Beca Ortiz
de Landázuri” as the best research clinical project in
2014, as well as by a research grant PI17/01814 of
the Ministerio de Economía, Industria y
Competitividad (ISCIII, FEDER). Dr Lucia is funded
by ISCIII and Fondos FEDER (PI15/00558).
Role of the Funder/Sponsor:The Gobierno de
Navarra had no role in the design and conduct of
the study; collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Additional Contributions: We thank Fundacion
Miguel Servet (Navarrabiomed) for its support
during the implementation of the trial, as well as
Fundación Caja Navarra and Fundación La Caixa.
Finally,we thank our patients and their families for
their confidence in the research team.
Additional Contributions: We thank the patients
depicted in the videos for granting permission to
publish this information.
REFERENCES
1. Rechel B, Grundy E, Robine JM, et al. Ageing in
the European Union. Lancet. 2013;381(9874):1312-
1322. doi:10.1016/S0140-6736(12)62087-X
2. World Health Organization. World report on
ageing and health: 2015. http://www.who.int
/ageing/events/world-report-2015-launch/en/.
Accessed July 13, 2018.
3. Spillman BC, Lubitz J. The effect of longevity on
spending for acute and long-term care. N Engl J Med.
2000;342(19):1409-1415. doi:10.1056
/NEJM200005113421906
4. Gilbert T, Neuburger J, Kraindler J, et al.
Development and validation of a Hospital Frailty
Risk Score focusing on older people in acute care
settings using electronic hospital records: an
observational study.Lancet. 2018;391(10132):1775-
1782. doi:10.1016/S0140-6736(18)30668-8
5. Gill TM, Gahbauer EA, Han L, Allore HG. The role
of intervening hospital admissions on trajectories of
disability in the last year of life: prospective cohort
study of older people. BMJ. 2015;350:h2361.
doi:10.1136/bmj.h2361
6. Martínez-Velilla N, Herrero AC, Cadore EL, Sáez
de Asteasu ML, Izquierdo M. Iatrogenic nosocomial
disability diagnosis and prevention. J Am Med Dir
Assoc. 2016;17(8):762-764. doi:10.1016/j.jamda.2016
.05.019
7. Gill TM, Allore HG, Gahbauer EA, Murphy TE.
Change in disability after hospitalization or
restricted activity in older persons. JAMA. 2010;
304(17):1919-1928. doi:10.1001/jama.2010.1568
8. Boyd CM, Landefeld CS, Counsell SR, et al.
Recovery of activities of daily living in older adults
after hospitalization for acute medical illness. JAm
Geriatr Soc. 2008;56(12):2171-2179. doi:10.1111
/j.1532-5415.2008.02023.x
9. Brown CJ, Redden DT,Flood KL, Allman RM. The
underrecognized epidemic of low mobility during
hospitalization of older adults. J Am Geriatr Soc.
2009;57(9):1660-1665. doi:10.1111/j.1532-5415.2009
.02393.x
Effect of Exercise Intervention on Functional Decline in Very Elderly Patients Original Investigation Research
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online November 12, 2018 E7
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
10. Martínez-Velilla N, Urbistondo-Lasa G,
Veintemilla-Erice E, Cambra-Contín K. Determining
the hours hospitalised patients are bedridden due
to their medical condition and functional
impairment and secondary mortality [in Spanish].
Rev Esp Geriatr Gerontol. 2013;48(2):96.
11. Ehlenbach WJ, Hough CL, Crane PK, et al.
Association between acute care and critical illness
hospitalization and cognitive function in older
adults. JAMA. 2010;303(8):763-770.doi:10.1001
/jama.2010.167
12. Baztán JJ, Suárez-García FM, López-Arrieta J,
Rodríguez-Mañas L, Rodríguez-Artalejo F.
Effectiveness of acute geriatric units on functional
decline, living at home, and case fatality among
older patients admitted to hospital for acute
medical disorders: meta-analysis. BMJ. 2009;338:
b50. doi:10.1136/bmj.b50
13. Ellis G, Whitehead MA, O’Neill D, Langhorne P,
Robinson D. Comprehensive geriatric assessment
for older adults admitted to hospital. Cochrane
Database Syst Rev. 2011;(7):CD006211.
14. Greysen SR. Activating hospitalized older
patients to confront the epidemic of low mobility.
JAMA Intern Med. 2016;176(7):928-929.
doi:10.1001/jamainternmed.2016.1874
15. de Morton NA, Keating JL, Jeffs K. Exercise for
acutely hospitalised older medical patients.
Cochrane Database Syst Rev. 2007;(1):CD005955.
16. Brown CJ, Foley KT,Lowman JD Jr, et al.
Comparison of posthospitalization function and
community mobility in hospital mobility program
and usual care patients: a randomized clinical trial.
JAMA Intern Med. 2016;176(7):921-927. doi:10.1001
/jamainternmed.2016.1870
17. Cadore EL, Casas-Herrero A, Zambom-Ferraresi
F, et al. Multicomponent exercisesincluding muscle
power training enhance muscle mass, power
output, and functional outcomes in
institutionalized frail nonagenarians. Age (Dordr).
2014;36(2):773-785. doi:10.1007/s11357-013-9586-z
18. Loyd C, Beasley TM, Miltner RS, Clark D, King B,
Brown CJ. Trajectories of community mobility
recovery after hospitalization in older adults. JAm
Geriatr Soc. 2018. doi:10.1111/jgs.15397
19. Chan AW, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT
2013 explanation and elaboration: guidance for
protocols of clinical trials. BMJ. 2013;346:e7586.
doi:10.1136/bmj.e7586
20. Moher D, Schulz KF, Altman DG; CONSORT.
The CONSORT statement: revised
recommendations for improving the quality of
reports of parallel group randomized trials.
BMC Med Res Methodol. 2001;1:2.
doi:10.1186/1471-2288-1-2
21. World Medical Association. World Medical
Association Declaration of Helsinki: ethical
principles for medical research involving human
subjects. JAMA. 2013;310(20):2191-2194.
doi:10.1001/jama.2013.281053
22. Mahoney FI, Barthel DW. Functional evaluation:
the Barthel Index. Md State Med J. 1965;14:61-65.
23. Martínez De La Iglesia J, Onís Vilches O, Dueñas
Herrero R, et al. The Spanish version of the
Yesavageabbreviated questionnaire (GDS) to
screen depressive dysfunctions in patients older
than 65 years: adaptation and validation [in
Spanish]. MEDIFAM. 2002;12:620-630.
24. Research Randomizer. http://www.randomizer
.org. Accessed February 1, 2018.
25. González-Saiz L, Fiuza-Luces C, Sanchis-Gomar
F, et al. Benefits of skeletal-muscle exercisetraining
in pulmonary arterial hypertension: the WHOLEi+12
trial. Int J Cardiol. 2017;231:277-283.doi:10.1016
/j.ijcard.2016.12.026
26. Izquierdo M, Casas-Herrero A,
Zambom-Ferraresi F, Martínez-VelillaN,
Alonso-Bouzón C, Rodríguez-Mañas L.
Multi-component physical exercise program
VIVIFRAIL. http://www.vivifrail.com/resources/send
/3-documents/23-e-book-interactive-pdf.
Published 2017. Accessed July 14, 2018.
27. Guralnik JM, Simonsick EM, Ferrucci L, et al.
A short physical performance battery assessing
lower extremity function: association with
self-reported disability and prediction of mortality
and nursing home admission. J Gerontol. 1994;49
(2):M85-M94. doi:10.1093/geronj/49.2.M85
28. Perera S, Mody SH, Woodman RC, Studenski
SA. Meaningful change and responsiveness in
common physical performance measures in older
adults. J Am Geriatr Soc. 2006;54(5):743-749.
doi:10.1111/j.1532-5415.2006.00701.x
29. van Bennekom CA, Jelles F, Lankhorst GJ,
Bouter LM. Responsiveness of the rehabilitation
activities profile and the Barthel Index. J Clin
Epidemiol. 1996;49(1):39-44. doi:10.1016/0895-4356
(95)00559-5
30. Shah S, Vanclay F, Cooper B. Improving the
sensitivity of the Barthel Index for stroke
rehabilitation. J Clin Epidemiol. 1989;42(8):703-709.
doi:10.1016/0895-4356(89)90065-6
31. Folstein MF, Folstein SE, McHugh PR.
“Mini-Mental State”: a practical method for grading
the cognitive state of patients for the clinician.
J Psychiatr Res. 1975;12(3):189-198. doi:10.1016
/0022-3956(75)90026-6
32. Badia X, Roset M, Montserrat S, Herdman M,
Segura A. The Spanish version of EuroQol:
a description and its applications: European Quality
of Life scale [in Spanish]. Med Clin (Barc). 1999;112
(suppl 1):79-85.
33. Laukkanen P, Heikkinen E, Kauppinen M.
Muscle strength and mobility as predictors of
survival in 75-84-year-old people. Age Ageing.
1995;24(6):468-473. doi:10.1093/ageing/24.6.468
34. Inouye SK, van Dyck CH, Alessi CA, Balkin S,
Siegal AP, Horwitz RI. Clarifying confusion: the
confusion assessment method: a new method for
detection of delirium. Ann Intern Med. 1990;113(12):
941-948. doi:10.7326/0003-4819-113-12-941
35. Van Ancum JM, Scheerman K, Jonkman NH,
et al. Change in muscle strength and muscle mass in
older hospitalized patients: a systematic review and
meta-analysis. Exp Gerontol. 2017;92:34-41.
doi:10.1016/j.exger.2017.03.006
36. Artero EG, Lee DC, Lavie CJ, et al. Effects of
muscular strength on cardiovascular risk factors
and prognosis. J Cardiopulm Rehabil Prev. 2012;32
(6):351-358. doi:10.1097/HCR.0b013e3182642688
37. Karlsen A, Loeb MR, Andersen KB, et al.
Improved functional performance in geriatric
patients during hospital stay.Am J Phys Med Rehabil.
2017;96(5):e78-e84.doi:10.1097/PHM
.0000000000000671
38. Rodriguez-Mañas L, Rodríguez-Artalejo F,
Sinclair AJ. The third transition: the clinical
evolution oriented to the contemporary older
patient. J Am Med Dir Assoc. 2017;18(1):8-9.
doi:10.1016/j.jamda.2016.10.005
39. Martínez-Velilla N, Cadore L, Casas-Herrero Á,
Idoate-Saralegui F, Izquierdo M. Physical activity
and early rehabilitation in hospitalized elderly
medical patients: systematic review of randomized
clinical trials. J Nutr Health Aging. 2016;20(7):738-751.
doi:10.1007/s12603-016-0683-4
40. Schweickert WD, Pohlman MC, Pohlman AS,
et al. Early physical and occupational therapy in
mechanically ventilated, critically ill patients:
a randomised controlled trial. Lancet. 2009;373
(9678):1874-1882. doi:10.1016/S0140-6736(09)
60658-9
41. Schaller SJ, Anstey M, Blobner M, et al;
International Early SOMS-guided Mobilization
Research Initiative. Early, goal-directed mobilisation
in the surgical intensive care unit: a randomised
controlled trial. Lancet. 2016;388(10052):1377-1388.
doi:10.1016/S0140-6736(16)31637-3
42. Gruther W, Pieber K, Steiner I, Hein C, Hiesmayr
JM, Paternostro-Sluga T. Can early rehabilitation on
the general ward after an intensive care unit stay
reduce hospital length of stay in survivors of critical
illness? a randomized controlled trial. AmJPhys
Med Rehabil. 2017;96(9):607-615. doi:10.1097
/PHM.0000000000000718
43. Sáez de Asteasu ML, Martínez-Velilla N,
Zambom-Ferraresi F, Casas-Herrero Á, Izquierdo M.
Role of physical exercise on cognitive function in
healthy older adults: a systematic review of
randomized clinical trials. Ageing Res Rev.2017;37:
117-134. doi:10.1016/j.arr.2017.05.007
44. Jeffs KJ, Berlowitz DJ, Grant S, et al. An
enhanced exercise and cognitive programme does
not appear to reduce incident delirium in
hospitalised patients: a randomised controlled trial.
BMJ Open. 2013;3(6):e002569. doi:10.1136
/bmjopen-2013-002569
45. McCusker J, Cole M, Dendukuri N, Belzile E,
Primeau F. Delirium in older medical inpatients and
subsequent cognitive and functional status:
a prospective study.CMAJ.2001;165(5):575-583.
Research Original Investigation Effect of Exercise Intervention on Functional Decline in Very Elderly Patients
E8 JAMAInternal Medicine Published online November 12, 2018 (Reprinted) jamainternalmedicine.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Departamento De Salud, Navarra User on 11/13/2018
