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Cochrane Database of Systematic Reviews

Protease activity as a prognostic factor for wound healing in venous leg ulcers

Overview of attention for article published in Cochrane database of systematic reviews, September 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (56th percentile)

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1 blog
14 X users
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1 Wikipedia page


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236 Mendeley
Protease activity as a prognostic factor for wound healing in venous leg ulcers
Published in
Cochrane database of systematic reviews, September 2018
DOI 10.1002/14651858.cd012841.pub2
Pubmed ID

Maggie J Westby, Jo C Dumville, Nikki Stubbs, Gill Norman, Jason KF Wong, Nicky Cullum, Richard D Riley


Venous leg ulcers (VLUs) are a common type of complex wound that have a negative impact on people's lives and incur high costs for health services and society. It has been suggested that prolonged high levels of protease activity in the later stages of the healing of chronic wounds may be associated with delayed healing. Protease modulating treatments have been developed which seek to modulate protease activity and thereby promote healing in chronic wounds. To determine whether protease activity is an independent prognostic factor for the healing of venous leg ulcers. In February 2018, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase and CINAHL. We included prospective and retrospective longitudinal studies with any follow-up period that recruited people with VLUs and investigated whether protease activity in wound fluid was associated with future healing of VLUs. We included randomised controlled trials (RCTs) analysed as cohort studies, provided interventions were taken into account in the analysis, and case-control studies if there were no available cohort studies. We also included prediction model studies provided they reported separately associations of individual prognostic factors (protease activity) with healing. Studies of any type of protease or combination of proteases were eligible, including proteases from bacteria, and the prognostic factor could be examined as a continuous or categorical variable; any cut-off point was permitted. The primary outcomes were time to healing (survival analysis) and the proportion of people with ulcers completely healed; the secondary outcome was change in ulcer size/rate of wound closure. We extracted unadjusted (simple) and adjusted (multivariable) associations between the prognostic factor and healing. Two review authors independently assessed studies for inclusion at each stage, and undertook data extraction, assessment of risk of bias and GRADE assessment. We collected association statistics where available. No study reported adjusted analyses: instead we collected unadjusted results or calculated association measures from raw data. We calculated risk ratios when both outcome and prognostic factor were dichotomous variables. When the prognostic factor was reported as continuous data and healing outcomes were dichotomous, we either performed regression analysis or analysed the impact of healing on protease levels, analysing as the standardised mean difference. When both prognostic factor and outcome were continuous data, we reported correlation coefficients or calculated them from individual participant data.We displayed all results on forest plots to give an overall visual representation. We planned to conduct meta-analyses where this was appropriate, otherwise we summarised narratively. We included 19 studies comprising 21 cohorts involving 646 participants. Only 11 studies (13 cohorts, 522 participants) had data available for analysis. Of these, five were prospective cohort studies, four were RCTs and two had a type of case-control design. Follow-up time ranged from four to 36 weeks. Studies covered 10 different matrix metalloproteases (MMPs) and two serine proteases (human neutrophil elastase and urokinase-type plasminogen activators). Two studies recorded complete healing as an outcome; other studies recorded partial healing measures. There was clinical and methodological heterogeneity across studies; for example, in the definition of healing, the type of protease and its measurement, the distribution of active and bound protease species, the types of treatment and the reporting of results. Therefore, meta-analysis was not performed. No study had conducted multivariable analyses and all included evidence was of very low certainty because of the lack of adjustment for confounders, the high risk of bias for all studies except one, imprecision around the measures of association and inconsistency in the direction of association. Collectively the research indicated complete uncertainty as to the association between protease activity and VLU healing. This review identified very low validity evidence regarding any association between protease activity and VLU healing and there is complete uncertainty regarding the relationship. The review offers information for both future research and systematic review methodology.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 236 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 236 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 41 17%
Student > Master 38 16%
Researcher 17 7%
Student > Ph. D. Student 17 7%
Student > Doctoral Student 13 6%
Other 34 14%
Unknown 76 32%
Readers by discipline Count As %
Medicine and Dentistry 69 29%
Nursing and Health Professions 27 11%
Biochemistry, Genetics and Molecular Biology 7 3%
Pharmacology, Toxicology and Pharmaceutical Science 7 3%
Agricultural and Biological Sciences 5 2%
Other 40 17%
Unknown 81 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 21. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 September 2022.
All research outputs
of 25,372,398 outputs
Outputs from Cochrane database of systematic reviews
of 12,220 outputs
Outputs of similar age
of 329,670 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 213 outputs
Altmetric has tracked 25,372,398 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,220 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 37.9. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,670 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 213 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.