Unravelling the potential mechanisms behind hospitalization-associated disability in older patients; the Hospital-Associated Disability and impact on daily Life (Hospital-ADL) cohort study protocol

Study design and setting

The Hospital-ADL study is a multicenter, observational, prospective cohort study designed
by an interdisciplinary team of researchers in the field of geriatrics, nursing, psychology,
physical therapy and rehabilitation. Six hospitals will participate: 1] the Academic
Medical Center in Amsterdam (AMC), a 1002-bed university teaching hospital; 2] the
Isala in Zwolle, a 994-bed regional teaching hospital; 3] the Tergooi in Blaricum,
a regional teaching hospital (633-bed spread over two sites: Hilversum and Blaricum);
4] the Slotervaart Hospital in Amsterdam, a 310-bed regional teaching hospital; 5]
the BovenIJ Hospital in Amsterdam, a 313-bed regional teaching hospital, and; 6] the
Meander Medical Center in Amersfoort, a 543-bed regional teaching hospital. The study
has started October 1, 2015 and will end after the last patient has been followed
up for three months post-discharge. We expect the recruitment phase to be completed
late 2016.

Patients

We aim to recruit 400 non-fully disabled adults aged ?70 years. The following inclusion
criteria apply: 1] acutely admitted at departments of Internal Medicine, Cardiology
or Geriatrics for 48 h or more in one of the above mentioned hospitals; 2] 70 years
and older; 3] have approval from the attending Medical Doctor for inclusion; 4] score
of 15 or higher on the Mini-Mental State Examination; 5] Dutch language proficiency
sufficient to complete questionnaires. Patients will be excluded if they: 1] have
a life expectancy of three months or less as assessed by the attending Medical Doctor,
or; 2] are disabled in all six basic ADL as determined by the Katz-ADL index 16].

Procedures

Eligible patients will be contacted, and the patient will be informed about the objectives
of this study and the study procedures, upon which written informed consent is obtained.
Furthermore, a legal representative of the patient will be contacted if the patient
has a MMSE score between 15 and 20. Two mobile geriatric assessment teams will visit
all six hospitals and will be present on Monday, Wednesday and Friday for consenting
and to perform assessments. The mobile geriatric assessment teams consist of a psychologist,
physical therapist, and/or a health scientist. The teams are trained in the study
procedures of obtaining informed consent, to perform assessments and physical performance
tests with adequate inter- and intra-rater reliability (0.8), and completing the
electronic case report form (eCRF).

Table 1 provides an overview of the location, content of assessment and duration of data
collection per time point. There will be at least five data collection points; within
48 h after admission (H
₁
), at discharge (H
₃
), and at one (P
₁
; home visit), two (P
_2;
by telephone) and three months (P
_3;
home visit) post-discharge. If the patient is admitted for more than five days, additional
measurements will be planned during hospitalization on Monday, Wednesday, and Friday
(i.e., the days that the mobile geriatric assessment team is present) (H
₂
),

Table 1. Time, location, content of assessment and duration of the Hospital-ADL study

Data will be collected through: 1] medical and demographical data (e.g., socio-demographic
characteristics, severity of acute illness, and geriatric-, and chronic conditions);
2] personal interviews (including cognitive, behavioral, psychosocial, and physical
parameters, and health care utilization, see description of information collected
below); 3] physical performance tests (e.g., gait speed, muscle strength, muscle mass,
mobility and physical functioning, see below) and; 4] blood samples (e.g., to assess
markers of inflammation).

The personal interviews will take place during hospitalization (H
₁
, H
₂
, and H
₃
), at the participant’s home or residence (P
₁
and P
₃
; one and three months post-discharge), and by telephone (P
₂
; two months post-discharge). Physical performance data will be collected within 48 h
after admission (H
₁
), during hospitalization on Monday, Wednesday and Friday (H
₂
), at discharge (H
₃
), and at one and three months post-discharge (P
₁
and P
₃
).

Primary outcome

The primary outcome is the level of ADL functioning three months post-discharge compared
to premorbid functioning, which are measured with the 6-item Katz-ADL index score
of the modified Katz-ADL index 17]. The Katz-ADL index score assesses the degree of independence in bathing, dressing,
toileting, use of incontinence materials, transfer from bed-chair and eating 16].

Secondary outcomes

Secondary outcomes include:

(1) Health care utilization (extension of the Minimal Dataset (MDS) 18] and Comprehensive Geriatric Assessment of the Transitional Care Bridge (TCB) 19], see below).

(2) Quality of life as measured with the EuroQol-5D 20] and the three items of the MDS 18] (see description below).

(3) Physical performance tests (see below for description of included tests).

(4) Mortality.

Scales and assessments

Table 2 gives a detailed overview of the primary and secondary outcomes at each time point.

(1)
Medical and demographical data

Socio-demographic characteristics. Socio-demographic data include age, gender, date and time of admission, highest level
of education, ethnicity, marital status and living arrangement.

Geriatric conditions. A comprehensive geriatric assessment (CGA) will be collected, which will provide
insight in the pre-illness determinants such as polypharmacy, substance use, incontinence,
and vision- and hearing impairments.

Chronic conditions. The number and severity of comorbidities will be scored with the Charlson Comorbidity
Index 21]. Depending on the risk of mortality, each condition is assigned a score of 1, 2,
3, or 6. Higher scores indicate a greater risk of mortality.

Severity of acute illness. The severity of the acute illness will be measured with the Modified Early Warning
Score (MEWS). The MEWS is based on 1] respiratory rate; 2] heart rate; 3] systolic
and diastolic blood pressure; 4] level of consciousness; 5] temperature, and; 6] oxygen
saturation 22].

Personal interviews/self-report data

(2.1) Cognitive functioning

Cognitive impairments. The most commonly used Mini Mental State Examination (MMSE) will be applied to classify
the severity of a cognitive impairment. It is a validated 23-item screening of cognitive
impairment. The MMSE consists of a series of questions and tests, which assess different
mental abilities, including memory, attention, language, and planning. Cognitive impairment
is defined as a score of 23 or less on the MMSE 23].

Delirium. The Confusion Assessment Method (CAM) will be used to identify the presence of delirium.
The CAM consists of four features: 1] acute onset and fluctuating course; 2] inattention;
3] disorganized thinking, and 4] altered level of consciousness. The diagnosis of
delirium requires the presence of both features 1 and 2, and the presence of either
feature 3 or 4 24]. Furthermore, we want to assess the risk for developing delirium with the following
statements of the Dutch Safety Management Programme (Veiligheidsmanagementsysteem (VMS)): 1] the patient needs help with self-care, 2] the patient has previously undergone
a delirium, and 3] the patient has a cognitive impairment such as dementia 25], 26].

(2.2) Behavioral and psychosocial functioning

Fear of falling. A Numeric Rating Scale (NRS) will be applied to measure fear of falling, in which
a participant selects a whole number (0–10 integers). Zero represents no fear of falling
and ten the worst possible fear of falling.

Depression. The Geriatric Depression Scale-15 (GDS-15) will be used to measure symptoms of depression
(Cronbach’s ??=?0.75 27]). The GDS-15 is a self-report scale of 15 items on a binary (yes/no) scale and assesses
symptoms over the preceding week. The total score is the sum of the 15 items (range
0–15 points, higher scores indicating more depression). The following categories of
the GDS-15 will be used: a score of 0 to 4 will be considered ‘normal’, a score of
5 to 8 a ‘mild depression’, 9 to 11 a ‘moderate depression’, and 12 to 15 a ‘severe
depression’ 28].

Apathy. Three items of the GDS-15 will be used to measure apathy (sensitivity of 69 % and
specificity of 85 % 29]). The three apathy items include the following questions: 1] “Do you prefer to stay
at home, rather than going out and doing new things?”; 2] “Have you dropped many of
your activities and interests?” and; 3] “Do you feel full of energy? Higher scores
indicate more apathy. A score of ?2 points is indicative for apathy 29].

Anxiety. The State-Trait Anxiety Inventory-6 (STAI-6) will be used to measure anxiety symptoms
(Cronbach’s ??=?0.79-0.81 30]). The STAI-6 is a short-form of the 20-item state scale of the Spielberger State-Trait
Anxiety Inventory (STAI) 31], that maintains results that are comparable with this full-form 30]. It consists of six items on a 4-point Likert scale (1] not at all/almost never;
2] somewhat/sometimes; 3] moderately so/often, and; 4] very much so/almost always).
Furthermore, it remains sensitive to different levels of anxiety.

Perceived self-efficacy. The General Self Efficacy Scale (In Dutch: Algemene Competentie Schaal (ALCOS-12)) will be used to measure general perceived self-efficacy (Cronbach’s ??=?0.78
32]). It is based on the Self-Efficacy Scale 33] and is a Dutch translated self-report rating scale of 12 items on a 5 point Likert
scale (1] strongly disagree; 2] disagree; 3] no disagreement/agreement; 4] agree and;
5] strongly agree). The ALCOS-12 includes three subscales: competence (Cronbach’s
??=?0.72), perseverance in adversity (Cronbach’s ??=?0.67), and taking initiative
(Cronbach’s ??=?0.74) 32]. The total score is the sum of the 12 items (range 12–60), whereby the following
categories of the ALCOS-12 will be used: a score of 12 to 38 will be defined as a
‘low competence level’, a score of 39 to 54 as ‘average’ and 55 to 60 as ‘high’ 34].

Health-Related Quality of life. The EuroQol-5D (EQ-5D), a widely used preference based generic health-related quality
of life (HRQoL) instrument with well-established psychometric properties will be administered
20]. The EQ-5D consists of five dimensions: 1] mobility; 2] self-care; 3] usual activities;
4] pain/discomfort and; 5] anxiety/depression. These dimensions have three response
choices (no problems; some problems or; severe problems). Moreover, the following
questions will be used to measure quality of life: 1] “In general, how is your quality
of life (participants answer the item with one of five possible responses: excellent;
very good; good; moderate or; bad)?”; 2] “How would you grade your life at this moment,
with a range between 0 and 10?” and; 3] “Compared to one year ago, how would you rate
your health in general now (five response choices: much better; slightly better; much
the same; slightly worse or; much worse)?” 18].

(2.3) Physical functioning

Dizziness, polynocturia and shortness of breath. Symptoms of dizziness and shortness of breath will be assessed by asking: “Do you
suffer from polynocturia/dizziness/shortness of breath at this moment? If yes, does
this affect your daily functioning?”

Pain. A gold standard of pain intensity measurements, the Numeric Rating Scale (NRS), will
be applied to measure pain. The NRS for pain is a validated continuous scale with
a score range between 0 and 10 (0 represents no pain and 10 the worst possible pain)
35], 36].

Fatigue. The Numeric Rating Scale (NRS), will be used to measure fatigue. The NRS for fatigue
is a continuous scale with a score range between zero and ten (zero represents no
pain and ten the worst possible fatigue) 37].

Impact of fatigue. The abbreviated version of the 21-item Modified Fatigue Impact Scale (MFIS) will
be used to quantify the impact of fatigue. The short version consists of five items
that are divided into three subscales: physical- (2 items), cognitive- (2 items),
and psychosocial functioning (1 item) subscale. An example of a MFIS-5 statement is:
“Because of my fatigue during the past four week, I have been less alert.” The total
score of the MFIS-5 is the sum of the raw scores on a 5-point Likert scale (0] never;
1] rarely; 2] sometimes; 3] often, and; 4] almost always). Higher scores indicate
greater fatigue 38].

Sleep. The Pittsburgh Sleep Quality Index (PSQI) will be utilized to measure two components
of sleep: sleep quality and sleep medication. Sleep quality will be quantified by
asking: “During the past month, how would you rate your sleep quality overall?” Sleep
medication will be measured by asking: “During the past month, how often have you
taken medicine (prescribed or “over the counter”) to help you sleep?” The score of
sleep quality and sleep medication have a range of 0 (better) to 3 (worse) 39]. In addition, we measure daily sleepiness on a binary scale (yes/no) with the following
question: “Do you currently suffer from daytime sleepiness? If yes, does this affect
your daily living?”

Nutrition. The widely used Short Nutritional Assessment Questionnaire (SNAQ) will be applied
to identify malnourished hospital patients (Cronbach’s alpha?=?0.58 40]) 25], 26]. The total score of the SNAQ is the sum of the raw scores, whereby the following
categories of the SNAQ will be used: a score of 0 to 1 will be defined as ‘no malnutrition’,
a score of 2 as ‘moderate malnutrition’ and a score of 3 as ‘severe malnutrition’
41].

ADL functioning. The 15 items modified Katz-ADL index will be used to measure physical functioning
16], 17]. The modified Katz-ADL index consists of statements of their independency in performing
basic Activities of Daily Living (ADL) and Instrumental Activities of Daily Living
(IADL) (formulated in two versions on a binary (yes/no) scale: two weeks before admission
or currently).

Mobility. The Functional Ambulation Categories (FAC) will be used to classify mobility, using
six categories: a category of 1 will be defined as ‘independent unlimited’, a category
of 2 as ‘independent limited’ and categories 3 to 5 as ‘dependent’. Allocation to
these last categories is based on levels of assistance and supervision needed 42]. Furthermore, we will measure mobility with two questions in according to the Comprehensive
Geriatric Assessment (CGA) of the Dutch Society of Clinical Geriatrics (NVKG, 2012):
1] “Were you able to walk outside the house for five minutes (formulated in two versions:
two weeks before admission or currently)?”, and; 2] “How often did/do you perform
physical activity two weeks before admission/currently 19]?”

Falls. To measure the number of falls in the past (six) month(s) the following question
of the VMS will be used: “Have you fallen once or more in the past (six) month(s)?
If yes, how many times 25], 26]?”

(2.4) Health care utilization

(Re)admission(s). Any (re)admission(s) to the hospital will be measured. We will search the medical
record for (re)admission(s) in the same hospital six months before hospitalization
and during three months post-discharge, and we will also retrieve this information
by self-report at P
₁
-P
₃
with the following self-report question: “Have you been hospitalized in the last month?
If yes, for how many days 18]?” Data that will be collected out of the hospital system are: date of admission and
discharge for any readmission, whether the admission was planned or unplanned and
the reason for the readmission.

Nursing home admission(s). The amount of nursing home admission or whether they were admitted to the nursing
home and the length of stay will be measured with the subsequent question: “Have you
had a nursing home admission in the last month? If yes, for how many weeks totally
18]?”

Consult of physical therapist and/or occupational therapist. The amount of consults of a physiotherapist and/or occupational therapist will be
measured by asking: “Have you had a consultation with your physical therapist and/or
occupational therapist in the last month? If yes, how many times?”

Consult general practitioner. The amount of consults of a general practitioner will be measured by asking: “Have
you had a consultation with your general practitioner in the last month? If yes, in
the evening, night or weekend and how many times in total 19]?”

Home care. The use of home care will be measured with the subsequent question: “Do you use home
care? If yes, care assistance and/or domestic help and how many hours per week 19]?” A distinction will be made between household help from a nursing aid, and help
from a registered nurse.

(2)
Physical performance tests

Handgrip strength. The hand grip strength will be measured with the widely used Jamar® grip strength
dynamometer (Lafayette Instrument Company, USA). The handgrip strength test is used
to provide an objective index of general upper body strength. Handgrip strength is
a reliable instrument (good to excellent test-retest reproducibility and excellent
inter-rater reliability) to indicate skeletal muscle mass 43]. Participants will perform the task thrice with each hand. The highest score from
either hand will be used and registered in the eCRF. Normative values of adults are
described in a study of Mathiowetz 44].

Mobility. To measure the mobility we will use the 15-item Morton Mobility Index (DEMMI). Subjects
will be asked to perform several mobility tasks, in the order of bed, chair, stand,
and walking activities to maximize patient safety, which will result in an ordinal
raw score (range: 0–19). The ordinal raw score will be converted into a total interval
DEMMI score (range: 0 to 100 points). Moreover, the DEMMI has a hierarchical structure,
and thus each assessed participant can be evaluated. Higher scores indicate a better
mobility performance 45].

Balance, strength, and gait speed. The Short Physical Performance Battery (SPPB) will be applied to measure the balance,
strength and gait speed. Participants will be asked to stand with their feet in various
balance positions, walk a distance of four meter and to rise from a chair and return
to the seated position five times as quickly as possible. Higher scores indicate a
better performance 46].

Back and hamstring flexibility. The Chair Sit and Reach (CSR) test will be used as a measure of flexibility. Participant
will be asked to extend one leg as straight as possible, hands on top of each other,
and then to reach to his/her foot as far as possible. Lower distances between the
tip of his/her toes and their extended fingers indicating a higher back and hamstring
flexibility 47], 48].

Walking distance. The 2 Minute Walking West (2MWT) will be applied to measure the maximal walking distance
in meters. Participants will be asked to walk back and forth along a premeasured corridor
of 15 meter in two minutes. Longer walking distances indicating a better walking capacity
49].

Body composition. The Bioelectrical Impedance Analysis (BIA) (Bodystat Quadscan 4000) will be used
as method for estimating body composition, in particular fat-free mass (FFM) and high
fat mass (FM). Electrodes will be attached to the ankle and wrist. A small electric
signal will circulate, which measures the resistance and reactance of this electrical
signal in the human body 50].

Activity level. The Fitbit Flex will be applied to monitor the sleep quality, measure motion patterns,
determine the calories burned, distance traveled, and steps taken 51]. Participants will be asked to wear the Fitbit Flex from hospital admission up to
one and a half weeks post-discharge.

(3)
Blood parameters

Inflammation markers. Inflammation markers, such as C-Reactive Protein (CRP) 52], Tumor Necrosis Factor-? (TNF-?), the interleukins IL-6 53]–55] and IL-8) 55], and White Blood Cell Differential (WBC diff), will be determined from blood plasma
and serum. Blood will be collected during the customary laboratory rounds during hospitalization.
Venous blood will be collected in 4.5 ml EDTA and serum vacutainers. Samples will
be centrifuged and stored at ?80 C° until analysis. Sample handling and analyses will
be performed according to ISO standards.

Table 2. Summary of outcome measures and time points of assessment in Hospital-ADL study

Planned statistical analyses

Data will be analyzed in accordance with the research questions outlined in the introduction,
applying appropriate General Linear Models (e.g., linear regression, repeated measures
ANOVA/ANCOVA) as well as log-linear models (e.g., logistic regression in case of binary
outcomes). Mortality, a (censored) numerical outcome, will be tested using survival
analysis. The global ? level will be set at 0.05 with hypothesis-wise adjustment for
multiple testing. All analyses will be performed using SPSS version 22.0 56]. Castor Electronic Data Capture (EDC) will be used to build electronic Case Report
Forms (eCRFs) for save and valid data collection.

Primary endpoint in the study will be HAD as measured with the Katz-ADL index score.
For multivariable analyses (General Linear models and log-linear models) a custom
10:1 case-to-outcome ratio is utilized as a maximum. Utilizing a repeated measures
design, power calculations imputing a conservative ? level of 0.01 yielded a power
of 95 % for associations of a small effect-size (Cohen’s f?=?0.069), whereas a power
of 80 % was established for associations with an effect-size of 0.058 (Cohen’s f).