Effectiveness of the RISE Intervention

Major Adverse Cardiovascular Events (MACE)

MACE, a composite of clinical end points of recurrent stroke or Transcient Ischaemic Attack (TIA) (definition in American Heart Association guidelines (44)), acute coronary events, and cardiovascular death. Stroke recurrence will be diagnosed by acute neurological symptoms and signs, and confirmed by magnetic resonance imaging. Acute coronary events (myocardial infarction (MI), cardiac revascularization, hospitalization with unstable angina) are diagnosed according to Consensus Conference of the European College of Cardiology and American College of Cardiology criteria (45). Deaths are regarded to be attributable to a cardiovascular cause (fatal MI, fatal stroke (i.e. death within 1 month of MI or stroke), sudden death caused by definite coronary artery disease, congestive heart failure) unless a non-cardiac death could be confirmed. This information about MACE will be collected at T1, T2, T3 and T4 using patient records from general practitioners and a questionnaire to participants.

Cost-Effectiveness

Assessed for MACE and quality adjusted life years (QALYs). QALYs will be based on the patients' responses to EQ 5D-5L (46). These responses will be converted into utility values using the Dutch tariff , after which QALYs will be estimated using linear interpolation between measurement points (47). All costs related to the RISE intervention will be considered: costs of intervention, other healthcare, informal care, sports, unpaid productivity, absenteeism, and presenteeism costs. Intervention costs will be micro-costed, meaning that detailed data will be gathered about the number and kinds of resources are used while providing the RISE intervention as well as information about their respective unit costs. All other costs will be measured at T0-T4 using modified versions of the iMTA Medical Consumption Questionnaire (iMCQ) and the iMTA Productivity Cost Questionnaire (iPCQ) (48). In accordance with the Dutch manual for costing studies in health care

Quality of life

Health Related Quality of Life will be measured with the EuroQol-5D (EQ-5D) (50, 51) at T0, T1, T2, T3 and T4. This questionnaire comprises of 5 dimensions i.e., mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Per dimension, patients are asked to indicate their health status on a 5-point Likert scale (1 = no problems; 5 = extreme problems). The health states can be converted into utility units by means of the Dutch rates (52). Utilities represent quality of life into a single number that ranges from 0 (death) to 1 (full health). Quality Adjusted Life Years (QALY's) can subsequently be calculated by multiplying the patients' utilities by the duration of time they spent in that particular health status.

Patients' healthcare utilization and patients' (unpaid) productivity losses

Patients' healthcare utilization and patients' (unpaid) productivity losses will be measured using cost questionnaires. There will be made use of retrospective 3-month cost questionnaires (at T1, T2, T3 and T4) to avoid recall bias. Healthcare utilization will be valued using Dutch standards costs (56). If these are unavailable, prices reported by professional organizations will be used. will be valued in accordance with the "Dutch Manual of Costing".

24-hour movement behaviour (sedentary behaviour, physical activity, sleep)

24-hour movement behaviour consists of movement behaviour (sedentary time and physical activity) and sleep. 24-hour movement behaviour is measured with the ActivPAL (PAL Technologies Ltd, Glasgow, United Kingdom) at T0, T1, T2 and T4 (34). This monitor is combination of a triaxial accelerometer and inclinometer, worn on the anterior side of the unaffected thigh, and detects if someone is either sedentary (sitting, lying or reclining), standing or walking. The ActivPAL is sealed in a waterproof sleeve and attached to the skin using hypoallergic tape. Participants are instructed to wear the ActivPAL for eight consecutive days. The first 24 hour of the data will be removed in order to counteract a possible Hawhorne effect (53). This ActivPAL is reliable (Intraclass correlation coefficient 0.79-0.99) and valid (98-100% accuracy) for measuring sedentary time and posture transitions during daily life in people with stroke (41-43).

Safety during the RISE intervention and follow-up measurements.

Safety will be objectified by the number of adverse events registered by the researcher during the intervention and/or during the follow-up measurements following the registration process (T0, T1, T2, T3, T4).

Physical functioning and participation

Physical functioning and participation, measured with the Short Physical Performance Battery (SPPB) at T0 and T1. THE SPPB is an objective assessment tool for evaluating lower extremity functioning in older persons, which gives insight in someone's walking speed, balance and leg strength. The SPPB consists of a balance test, a gait speed test and a chair stand test, of which each item is score with 1, 2 or 4 points. The maximal total score is 12, in which a higher score indicates better lower extremity functioning. The SPPB has an excellent interrater reliability (Intraclass Correlatin Coefficient (ICC) = 0.81 to 0.91) and excellent test-retest reliability (ICC = 0.84). (54, 55). The validity of the SPPB for measuring lower extremity function is moderate to high (0.66-0.79) (56).

Sleep quality and quantity

Sleep quality and quantity, measured with Emfit sleep tracker, at T0, T1, T2 and T4. The Emfit QS sleep tracker (Emfit Ltd, Vaajakoski, Finland; 542 3 70 3 1.4 mm) has recently been validated in healthy adult participants using an electrocardiography based reference device. The Emfit QS showed good validity and reliability in measuring heart rate during the sleep period (57). Next to the Emfit QS, experienced sleep quality is measured with the Pittsburgh Sleep Quality Index (PSQI). The PSQI is a 19-item self-reported questionnaire about experienced sleep quality in the past month. The PSQI shows a structural validity ranging between 0.70 and 0.83 (58).

Fatigue

Level of fatigue, is according to the Stroke Recovery Roundtable on fatigue, measured with the Fatigue Severity Scale-7 (FSS-7) and Visual Analogue Scale at T0, T1, T2 and T4. The items are asked about the past few weeks and relate to the perceived severity offatigue in different daily situations. The FSS-7 measures chronic fatigue in 7 items with a 7-point likert scale (ranging from 'totally disagree' to 'totally agree'). The final score is the mean of the 7 item scores. A final score of ≥4 indicates that the severity of fatigue has a medium to high impact on daily life. The FSS-7 demonstrates excellent item-reliability (Cronbach's alpha 0.87-0.93) in measuring change in fatigue over time (59).