Evie Gardner

Keratinocyte growth factor for the treatment of the acute respiratory distress syndrome (KARE): a randomised, double-blind, placebo-controlled phase 2 trial

BACKGROUND Data from in-vitro, animal, and human lung injury models suggest that keratinocyte growth factor (KGF) might be beneficial in acute respiratory distress syndrome (ARDS). The objective of this trial was to investigate the effect of KGF in patients with ARDS. METHODS We did a double-blind, allocation concealed, randomised, placebo-controlled phase 2 trial in two intensive care units in the UK, involving patients fulfilling the American-European Consensus Conference Definition of ARDS. Patients were randomly assigned (1:1) by computer-generated randomisation schedule with variable block size stratified by site and presence of severe sepsis requiring vasopressors to receive either recombinant human KGF (palifermin 60 μg/kg) or placebo (0·9% sodium chloride solution) daily for a maximum of 6 days. Both patients and investigators were masked to treatment. The primary endpoint was oxygenation index (OI) at day 7. Analyses were by intention to treat. The trial is registered with International Standard Randomised Controlled Trial Registry, number ISRCTN95690673. FINDINGS Between Feb 23, 2011, and Feb 26, 2014, 368 patients were assessed for eligibility for inclusion in the trial. Of the 60 patients recruited, 29 patients were randomly assigned to receive KGF and 31 to placebo; all were included in the analysis of the primary outcome. There was no significant difference between the two groups in OI at day 7 (mean 62·3 [SD 57·8] in the KGF group, 43·1 [33·5] in the placebo group; mean difference 19·2, 95% CI -5·6 to 44·0, p=0·13). Of interest, although not defined as outcome measures a priori, the KGF group, compared with placebo, had fewer median ventilator-free days (1 day [IQR 0 to 17] in the KGF group vs 20 days [13-22] in the placebo group; difference -8 days, 95% CI -17 to -2; p=0·0002), a longer median duration of ventilation in survivors to day 90 (16 days [IQR 13-30] in the KGF group vs 11 days [8-16] in the placebo group; difference 6 days, 95% CI 2 to 14; p=0·002), and a higher mortality at 28 days (nine [31%] vs three [10%] deaths; risk ratio 3·2, 95% CI 1·0 to 10·7, p=0·054). Adverse events were more frequent in the KGF group than the placebo group (14 vs 5 events; odds ratio 4·9, 95% CI 1·3 to 20·3, p=0·008). The two adverse events assessed as related to KGF were due to pyrexia. INTERPRETATION KGF did not improve physiological or clinical outcomes in ARDS and might be harmful to patient health. FUNDING The Northern Ireland Public Health Agency Research and Development Division.

Spinal cord injury and pressure ulcer prevention: using functional activity in pressure relief.

Background. People with spinal cord injury (SCI) are at increased risk of pressure ulcers due to prolonged periods of sitting. Concordance with pressure relieving movements is poor amongst this population, and one potential alternative to improve this would be to integrate pressure relieving movements into everyday functional activities. Objectives. To investigate both the current pressure relieving behaviours of SCI individuals during computer use and the application of an ergonomically adapted computer-based activity to reduce interface pressure. Design. Observational and repeated measures design. Setting. Regional Spinal Cord Injury Unit. Participants. Fourteen subjects diagnosed with SCI (12 male, 2 female). Intervention.Comparing normal sitting to seated movements and induced forward reaching positions. Main Outcome Measures. Interface pressure measurements: dispersion index (DI), peak pressure index (PPI), and total contact area (CA). The angle of trunk tilt was also measured. Results. The majority of movements yielded less than 25% reduction in interface pressure compared to normal sitting. Reaching forward by 150% of arm length during an adapted computer activity significantly reduced DI (P < 0.05), angle of trunk tilt (p<0.05), and PPI for both ischial tuberosity regions (P < 0.001) compared to normal sitting. Conclusion. Reaching forward significantly redistributed pressure at the seating interface, as evidenced by the change in interface pressures compared to upright sitting.

Effectiveness of an exercise programme on physical function in patients discharged from hospital following critical illness: a randomised controlled trial (the REVIVE trial)

Objective To investigate the effectiveness of a 6-week exercise programme in patients discharged home following critical illness compared with standard care. Design Multicentre prospective phase II randomised controlled trial, with blinded outcome assessment after hospital discharge, following the 6-week intervention and at 6 months. Participants 60 patients (30 per group) aged ≥18 years, mechanically ventilated >96 hours, and not in other rehabilitation, that is, cardiac or pulmonary rehabilitation programmes. Participants in the intervention group completed an individually tailored (personalised) exercise programme. Outcome measures Primary outcome measure was SF-36 physical functioning following the intervention. Secondary outcomes included a range of performance-based and patient-reported measures. Results Improvements in the primary outcome did not differ significantly between groups (mean difference (95% CI) 3.0 (−2.2 to 8.2), p=0.26). The intervention group showed significant improvement compared with the control group (mean difference (95% CI)) in SF-36 role physical (6.6 (0.73 to 12.5), p=0.03); incremental shuttle walk test (83.1 m (8.3 to 157.9), p=0.03); functional limitations profile (−4.8 (−8.7 to −0.9), p=0.02); self-efficacy to exercise (2.2 (0.8 to 3.7), p=0.01) and readiness to exercise (1.3 (0.8 to 1.9), p<0.001). These improvements were not sustained at 6 months except readiness to exercise. Improvements in all other secondary outcome measures were not significant. Conclusions There was no statistically significant difference in the primary outcome measure of self-reported physical function following this 6-week exercise programme. Secondary outcome results will help inform future studies. Trial registration number NCT01463579. (results), https://clinicaltrials.gov/