2.4 Outcome
The primary outcome was time to first fall during follow-up. Falls were
defined as “an unintentional change in position resulting in coming to
rest at a lower level or on the ground” as recommended by the
Prevention of Falls Network Europe 17. Falls were
reported prospectively by using fall calendars, which the participants
filled in weekly and returned to the research team every three months.
Participants were contacted via telephone in case of missing or unclear
data. Participants were followed until their first fall incident until
their drop-out date or the date of their last calendar, date of death or
end of the study, which ever came first 14. We used
the data from fall calendars as a binary variable (yes/no) for the
analyses of plasma concentrations at follow-up and delta concentration.
Covariates
Participant data were collected at baseline and follow-up using a
questionnaire that included data on age, gender, smoking, alcohol
consumption, comorbidities and history of falls. During study visits,
data was collected on (self-reported) medication use, body mass index
(BMI), blood pressure, serum creatinine, physical performance, handgrip
strength, cognitive status, depressive symptoms and presence of pain.
For screening of depressive symptoms, the 15-item version of the
Geriatric Depression Scale (GDS-15) was used. Cognitive performance was
assessed by the mini-mental state examination (MMSE). For pain, the
EURoQoL-item 4 was used (pain or other complaints). Baseline use of
concomitant medication was grouped based on the ATC coding system, and
polypharmacy was defined as usage of five or more medications18. Serum creatinine levels were used to calculate
kidney function according to the Cockcroft and Gault formula.