The strata were diagnosis classification (medical or surgical) and mechanical selleck chem Sunitinib ventilation at day 5 (yes or no), creating four possible groups.Usual careIn both groups, physiotherapists provided both respiratory and mobility management based upon individual patient assessment [12] according to unit protocols. Administration of intravenous sedation in the ICU was titrated to achieve a Richmond Agitation Sedation Scale score between ?1 and +1 [16] for each patient. In the usual-care arm, mobility may have included active bed exercises, sitting out of bed and/or marching or walking. Usual care was available 7 days per week for 12 hours per day. Acute ward physiotherapy services emphasized functional recovery and discharge planning. Outpatient exercise classes for ICU survivors were not included in usual-care physiotherapy at the hospital.

Intervention armIntervention was individualized based upon participant level and results of baseline physical function tests [17]. The criteria for safety and ceasing the intervention were set a priori and published previously in the protocol paper [11]. An overview of intervention in ICU, on the acute ward and in outpatients is provided in Table 1 and the Additional file 1. The intervention was designed to provide more active functional rehabilitation based upon physiological principles of exercise prescription, in all phases of the study than would be received as part of usual care. The timing of outcomes post hospital discharge are given in Figure 1.Table 1Exercise rehabilitation in ICU, ward and outpatient settingsaFigure 1Participant flow through the trial.

Statistical analysesThe study was designed to enroll 200 patients to provide a statistical power of 80% to detect a mean difference in 6MWT at 6 months of 50 m using a standard deviation of 110 m, including allowance for loss to follow-up [18]. All descriptive data were analyzed using SPSS for Windows version 18.0 software (SPSS, Chicago, IL, USA). Analyses of the outcome data were performed using SAS for Windows version 9.3 software (SAS Institute, Inc, Cary, NC, USA). The primary outcome (6MWT) was analyzed on the basis of a linear mixed model with group (usual care or intervention) and time (treated as categorical with levels at ICU discharge, hospital discharge, and 3, 6 and 12 months post�CICU discharge).

Linear mixed models use all data available at each time point; thus missing data imputation was not undertaken. Stratification factors (diagnosis classification: medical or surgical, mechanical ventilation at day 5 yes or no) were also included as covariates by adding them to the regression model. A similar approach was Drug_discovery used for the secondary outcomes (TUG, AQoL and SF-36) and applied to all available data. Analyses were pragmatic and based on the intention-to-treat principle, which included data on all randomized participants with at least one outcome measure.