Study design and participants
The Delirium and Population Health Informatics Cohort (DELPHIC) study20,21 is a prospective population-based sample initiated in March 2017 in the borough of Camden (London, UK). Eligible participants were Camden residents aged ≥70 years. Participants were excluded if they had severe hearing impairment or aphasia, were in the terminal phase of illness (expected life expectancy of <6 months), or could not speak English sufficiently well to undertake a cognitive assessment. Participants were primarily enrolled via general practitioner lists (80%) or, to include a greater range of cognitive impairment and frailty, from memory clinics (10%) and recent hospital discharges (10%). DELPHIC’s primary outcome was detecting a meaningful change in cognitive testing at a two-year follow-up. The protocol received approval from an NHS Research Ethics Committee (16/LO/1217) and the Health Research Authority (IRAS 164446).
Baseline health assessments were performed in the community by telephone or home visit, with identical follow-up two years later. Participants admitted to hospital were automatically flagged to be seen daily (excluding public holidays and weekends) by a trained clinical researcher. Several health variables were assessed daily in hospital, including mobility, cognition, and physiological measures. Individuals, or their nominated proxies, gave consent or agreement to participate. Death notification was from the NHS Spine, a statutory register for all deaths in England, and were cross-referenced with local hospital electronic records systems (last update 21st June 2021).
Measures
Frailty was measured at baseline and follow-up using a frailty index (FI)21,22 (Supplementary Table 1). This previously published FI, created using a standard process to ensure validity23, was modified to exclude mobility deficits. We did this to avoid collinearity with immobility burden, a relevant exposure in this study. The same items in both the baseline and follow-up frailty indices were used.
Mobility was assessed using the Hierarchical Assessment of Balance and Mobility (HABAM). The HABAM measures the highest daily attained performance in balance (21 points), transfers (18 points), and mobility (28 points), operating as an integrated measure of mobility. The HABAM was ascertained prospectively daily during hospitalisation. The mobility measured is functional, not intensity-based. Immobility was defined using the inverse of the HABAM, where higher scores indicate poorer mobility.24,25
We used the National Early Warning Score (NEWS, version 1) which is a composite scoring system that uses physiological measurements to assess and monitor acute illness severity in hospitalised patients.26 NEWS, a standard assessment tool mandated to be used at least daily by the NHS for all acute inpatient units, adds clinically abnormal indices (heart rate, blood pressure, respiratory rate, oxygen saturation, supplemental oxygen requirements, alertness), giving a score from 0 to 20. The index of multiple deprivation (2019) is an ecological measure of overall deprivation using 37 separate indicators across seven domains (income, employment, health, crime, education, barriers to services, and living environment). It is used throughout England and represents population sizes between 1200 and 3000 people.27
Statistical analysis
Outcome measure
Frailty: A frailty index was used to quantify baseline (exposure) and follow-up (outcome). Assuming an alpha of 0.05, a sample size of at least 82 hospitalisations would be required to detect the effect of immobility on mortality with a power of 80%.28
Exposures
Immobility burden: We quantified the total immobility burden during hospitalisation, measuring duration and severity, by summing daily immobility scores across inpatient assessments. This was additive across multiple admissions to include all immobility in the hospital during the two years of study enrollment. No mobility measurements were included following any transfer to subacute care units. No metrics were available on days individuals were waiting before transfer to subacute care.
Notionally, a low or high immobility burden could differentiate the type of hospital admission. As the HABAM had no established method to measure cumulative mobility burden during hospitalisation, we implemented the metric as follows: participants who were not hospitalised had no hospital immobility burden. Otherwise, for each participant, we calculated immobility burden by summing their daily HABAM scores across all hospital admissions. Hospitalised immobility burden was then dichotomised as high or low, based on the median score.
Missing data
In keeping with previous analyses, missing hospitalisation data during weekends and public holidays were assumed to be missing at random. Mobility data were forward and backfilled for weekends (Friday carried over to Saturday and data on Sunday from Monday) and public holidays for up to four days.21
Models
Frailty: We used linear regression to estimate the frailty index after two years in the study, adjusted by age, sex and baseline frailty). The main exposure was hospitalised immobility burden level (none/low/high) during the course of the 2-year study. Sensitivity analysis included excluding any participants with elective admissions, using immobility burden (continuous), mobility burden limited by the first 7 days of hospitalisation, correcting for baseline mobility status (mobility component of the Barthel Index), index of multiple deprivation and National Early Warning Score and only including those who were independently mobile at baseline assessment.
Additional analysis: Differences in baseline and follow-up mobility are reported to check for meaningful changes in mobility throughout the study that might be explained by immobility while not hospitalised.
We used R (4.0.2), Python (3.7.6) and Stata (17.0) for all analyses.