View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Keele Research Repository Cochrane Library Cochrane Database of Systematic Reviews Protease activity as a prognostic factor for wound healing in venous leg ulcers (Review) Westby MJ, Dumville JC, Stubbs N, Norman G, Wong JKF, Cullum N, Riley RD Westby MJ, Dumville JC, Stubbs N, Norman G, Wong JKF, Cullum N, Riley RD. Protease activity as a prognostic factor for wound healing in venous leg ulcers. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No.: CD012841. DOI: 10.1002/14651858.CD012841.pub2. www.cochranelibrary.com Protease activity as a prognostic factor for wound healing in venous leg ulcers (Review) Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Cochrane Trusted evidence. Informed decisions. Library Better health. Cochrane Database of Systematic Reviews T A B L E O F C O N T E N T S HEADER......................................................................................................................................................................................................... 1 ABSTRACT..................................................................................................................................................................................................... 1 PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2 BACKGROUND.............................................................................................................................................................................................. 4 OBJECTIVES.................................................................................................................................................................................................. 6 METHODS..................................................................................................................................................................................................... 6 Figure 1.................................................................................................................................................................................................. 9 RESULTS........................................................................................................................................................................................................ 12 Figure 2.................................................................................................................................................................................................. 15 Figure 3.................................................................................................................................................................................................. 16 Figure 4.................................................................................................................................................................................................. 18 Figure 5.................................................................................................................................................................................................. 19 Figure 6.................................................................................................................................................................................................. 20 Figure 7.................................................................................................................................................................................................. 20 DISCUSSION.................................................................................................................................................................................................. 21 AUTHORS' CONCLUSIONS........................................................................................................................................................................... 22 ACKNOWLEDGEMENTS................................................................................................................................................................................ 22 REFERENCES................................................................................................................................................................................................ 23 CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 35 DATA AND ANALYSES.................................................................................................................................................................................... 58 Analysis 1.1. Comparison 1 Protease activity continuous, Outcome 1 t-test assocation of protease level and healing 59 (dichotomous)....................................................................................................................................................................................... Analysis 1.2. Comparison 1 Protease activity continuous, Outcome 2 t-test association of protease level and healing: high (≥ 1 60 cmD/week) vs low (< 1 cmD/week) healing.......................................................................................................................................... Analysis 1.3. Comparison 1 Protease activity continuous, Outcome 3 Correlation coeGicients: protease levels and change in 60 size.......................................................................................................................................................................................................... Analysis 2.1. Comparison 2 Protease activity dichotomous, Outcome 1 Association of healing with elevated protease level; by 61 protease modulating (PM) intervention.............................................................................................................................................. APPENDICES................................................................................................................................................................................................. 62 Figure 8.................................................................................................................................................................................................. 71 Figure 9.................................................................................................................................................................................................. 72 Figure 10................................................................................................................................................................................................ 73 Figure 11................................................................................................................................................................................................ 74 Figure 12................................................................................................................................................................................................ 75 Figure 13................................................................................................................................................................................................ 76 CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 78 DECLARATIONS OF INTEREST..................................................................................................................................................................... 78 SOURCES OF SUPPORT............................................................................................................................................................................... 79 DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 79 INDEX TERMS............................................................................................................................................................................................... 79 Protease activity as a prognostic factor for wound healing in venous leg ulcers (Review) i Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Cochrane Trusted evidence. Informed decisions. Library Better health. Cochrane Database of Systematic Reviews [Prognosis Review] Protease activity as a prognostic factor for wound healing in venous leg ulcers Maggie J Westby1, Jo C Dumville1, Nikki Stubbs2, Gill Norman1, Jason KF Wong3, Nicky Cullum1, Richard D Riley4 1Division of Nursing, Midwifery and Social Work, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 2Leeds Community Healthcare NHS Trust, St Mary's Hospital, Leeds, UK. 3Manchester Centre for Plastic Surgery and Burns, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. 4Research Institute for