Patients and study design
We enrolled 20 older adults (age ≥ 50 years) in a prospective cohort study to assess the feasibility of a functional assessment for SCD. We later added an additional 20 younger adults (age 18-49 years) as a comparison group. Participants were enrolled from October 2018 to July 2020. Enrollment continued until we reached a target of 40 participants. We recruited participants from a single academic medical center in the Southeastern United States. We included participants that 1) have a diagnosis of SCD confirmed by hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), or genotyping and 2) speak fluent English. We excluded patients if they 1) were previously diagnosed with moderate to severe cognitive impairment by their usual outpatient providers, 2) were unable to self-consent, or 3) were wheelchair-bound at the time of recruitment. Participants were screened for eligibility by chart review and approached during routine clinic or sickle cell day hospital visits. No potential participants that were approached had to be excluded for cognitive impairment, inability to consent, language barriers, being wheelchair-bound, or inability to reach steady-state. The study was approved by the institutional review board. All participants provided written informed consent prior to enrollment.
Data Collection
Participants entered their demographics, complications from SCD, social history (e.g. education, annual household income, living arrangements, employment status), and healthcare utilization into a REDCap database. Investigators also recorded SCD complications, healthcare utilization, and steady-state laboratory values from the electronic medical record. All participants were assessed at steady-state, which we defined as greater than 6 weeks after their last hospitalization and greater than 2 weeks after their last emergency department (ED) or sickle cell day hospital visit. We confirmed participants were at steady-state by reviewing the medical record and asking the participant. We managed the data collection using REDCap electronic data capture tools.[19, 20] We included consensus measures from the Phenotypes and eXposures (PhenX) Toolkit when available.[21] Conflicts between self-report and investigator entered observations were handled by using medical history and healthcare utilization as documented in the electronic medical record.
Description of measures in the SCD-FA
The SCD-FA includes a combination of validated patient-reported questionnaires and performance-based measures administered by the study team (Table 1). This assessment focuses on key areas that are at the intersection of SCD and geriatrics collaboratively selected by SCD providers, geriatricians, and exercise specialists. We included measures from the oncology geriatric assessment developed by Hurria et al..[16, 17] Measures were originally selected based on validity, brevity, reliability, and prognostic value.[16, 17]
Table 1. Measures Selected for the Sickle Cell Disease Functional Assessment
Domains
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Measures in Each Domain
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Description
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Functional Status
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OARS Activities of Daily Living and Instrumental Activities of Daily Living
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Measures the extent to which one is able to function independently. Score Scores 0-28 with higher scores indicating more independence (14 items)
|
|
Physical Functioning Subscale of the SF-36
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Component of the 36-Item Short Form Health Survey (SF-36). Measures extent to which health currently limits daily activities. Scores range 0-100, with higher scores indicating better physical functioning (10 items)
|
|
Karnofsky performance status - self and physician*
|
Global measure of physical ability. Scores 0-100 with higher scores indicating better performance (2 items). Score ≥ 80 indicates good performance status.
|
|
Number of falls in last 6 months
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Self-reported number of falls in the last 6 months. ≥ 1 fall indicates increased risk of subsequent falls (1 item)
|
|
Usual Gait Speed*
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Comfortable walking pace on a 3-meter (10ft) course with an acceleration zone and deceleration zone. The fastest speed of 2 trials is used for the analysis. Scores compared to normative values based on age and gender.
|
|
Timed Up and Go*
|
The time it takes to rise from a standard height chair (46cm), walk a distance of 10 ft (3 meters), turn, walk back to the chair, and sit down again. Shortest time of 2 trials is used for the analysis. TUG assess balance. TUG > 10 seconds is associated with fractures in older adults and > 12 seconds indicates increased risk of falls
|
|
Dual-Task Performance*
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Assesses the effects of simultaneously performing a cognitive and motor task: usual walking speed for 1 minute and a verbal fluency task using letters F, A, and S. Each task performed once individually, then simultaneously twice using a different letter on each attempt. Scores are used to calculate whether cognitive-motor interference is present.
|
|
Six-Minute Walk Test*
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Distance walked in 6 minutes. 2-minute and 6-minute walking distances are recorded and heart rate recovery at 1 and 2 minutes. Scores compared to normative values based on age and gender.
|
|
Seated Grip Strength*
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Grip strength measured in triplicate alternating both hands using Jamar Technologies Hydraulic Hand Dynamometer while the participant remains seated in a standard height chair (46cm). Scores compared to normative values based on age and gender.
|
|
30-second Chair Stand*
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Number of times one can rise to a standing position and sit back down in 30 seconds. Scores compared to normative values based on age and gender.
|
Comorbid Medical Conditions
|
OARS Physical Health questionnaire
|
Patient-reported comorbidity checklist and the rated the degree to which the condition interferes with their daily activities (27 items)
|
Psychological State
|
Mental Health Inventory-18 (MHI-18)
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Includes anxiety, depression, behavioral control, and positive affect subscales. Total and subscale scores range 0-100, with higher scores indicating better mental health (18 items)
|
Social Support/ Social Activities
|
MOS Social Support Survey
|
Perceived availability of social support. Total score is on a 0-100 scale with lower scores indicating less support (19 items).
|
|
Social Functioning Subscale of the SF-36
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Measures amount of time physical health or emotional health interfered with social activities over the last 4 weeks. Subscale scores range from 0-100 with higher scores indicating better social functioning (1 item)
|
|
MOS Social Activity Limitations Measure
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Measures change in social activities and limitations in social activities compared to peers over the last 6 months. Mean of 2 items transformed to scores range 0-100 with higher scores indicating less limitations (2 items)
|
Nutritional Status
|
Body Mass Index
|
Calculated by measuring height and weight. A low BMI for older adults is <22 kg/m2 and obesity is ≥30 kg/m2 (1 item)
|
|
Unintentional Weight Loss
|
Unintentional weight loss in the last 6 months. Unintentional weight loss > 5% in 6-12 months is associated with increased mortality (1 item)
|
Cognition
|
Blessed Orientation-Memory-Concentration Test*
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Measures temporal orientation, short-term memory, and concentration. Weighted score ranges 0 to 28 with higher scores indicating more impairment. A score > 9 is concerning for cognitive impairment (6 items)
|
|
Montreal Cognitive Assessment*
|
Measures visuospatial skills, executive functions, memory, attention, calculation, concentration, language, abstraction, and orientation. On a scale of 0-30 with a score < 26 indicating cognitive impairment (16 items)
|
Medications
|
Comprehensive list of medications
|
Participant recorded medication list. Polypharmacy is defined as ≥ 5 prescribed medications.
|
OARS: Older Americans Resources and Services, MOS: Medical Outcome Study, SF-36: 36-item Short Form, TUG: Timed Up and Go, BMI: Body Mass Index
*Indicates performance-based measures that must be administered by personnel
The 7 domains of the SCD-FA are: functional status, comorbid medical conditions, psychological state, social support/social functioning, weight status, cognition, and patient-reported medication list. The oncology geriatric assessment included 3 provider-administered measures: Timed Up and Go (TUG), provider-reported Karnofsky Performance Status (KPS), and the Blessed Orientation Memory Concentration Test. We added 5 provider-administered physical performance measures to the TUG: usual gait speed, 6MWT with heart rate recovery, seated grip strength, 30-second chair stand, and dual-task performance (also includes cognitive component). We compared the results of each physical performance test to normative values based on age and gender where such data were available.[22] We added the Montreal Cognitive Assessment (MoCA) as an additional cognitive measure and the reading subtest of the Wide Range Achievement Test 5th Edition to account for differences in academic achievement beyond stated education level. For a detailed description of each measure see Table 1 and published protocol.[23]
Administering SCD-FA
Investigators who were SCD physicians received training and ongoing guidance on how to properly perform and analyze the physical function portions of the SCD-FA throughout the study. The SCD-FA was administered by first author and a trained research specialist in a quiet hallway in the sickle cell clinic.
Outcomes
The endpoints of this study are based on Consolidated Standards of Reporting Trials (CONSORT) extension to pilot and feasibility trials guidelines.[24, 25]
Primary Endpoint
The primary endpoint was the proportion of participants who completed the assessment in its entirety out of those that were consented. We defined feasibility as ≥ 80% of participants completing the SCD-FA.
Secondary Endpoints
The secondary endpoints were proportion consenting, duration of the SCD-FA, adverse events, and acceptability. We defined feasibility for these secondary endpoints as: 1) ≥ 80% providing written consent of those approached to participate, 2) a mean duration for completing the SCD-FA ≤ 120 minutes, 3) no moderate or severe adverse events within 48 hours after completing the SCD-FA.
We assessed acceptability of the SCD-FA with a satisfaction survey at the end of each study visit. We included questions about acceptability of the time it took to complete the entire assessment, whether questions were difficult to understand, uncomfortable, or upsetting, and if there were measures that should be added or removed. Acceptability was defined as < 20% reporting difficulties in understanding measures or reporting questions as upsetting or uncomfortable and at least 80% reporting the length of the SCD-FA as appropriate.
Statistical Analysis
We assessed feasibility overall and by age group by calculating proportions for each endpoint and the proportion of participants and individual measures with missing data. We described acceptability survey responses using simple descriptive statistics. Given that the primary purpose of this study is to evaluate feasibility, the remaining analyses were exploratory and descriptive in nature. We used descriptive statistics and visual displays to summarize the demographic data and unadjusted results of the SCD-FA measures. We compared the younger and older participants to age and sex-matched normative data. We determined an equivalent functional age by the comparing the mean physical performance score for each group by age and gender to expected normative values based on age and gender in the general population.[22, 26-29] Results were not interpreted as definitive in size or direction, or causal in their effect. We conducted analyses in R Statistical Software version 3.6.1 (Foundation for Statistical Computing, Vienna, Austria) and StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC.