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Cochrane Database of Systematic Reviews

Harms of off-label erythropoiesis-stimulating agents for critically ill people

Overview of attention for article published in Cochrane database of systematic reviews, August 2017
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  • Above-average Attention Score compared to outputs of the same age (53rd percentile)

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Harms of off-label erythropoiesis-stimulating agents for critically ill people
Published in
Cochrane database of systematic reviews, August 2017
DOI 10.1002/14651858.cd010969.pub2
Pubmed ID

Bita Mesgarpour, Benedikt H Heidinger, Dominik Roth, Susanne Schmitz, Cathal D Walsh, Harald Herkner


Anaemia is a common problem experienced by critically-ill people. Treatment with erythropoiesis-stimulating agents (ESAs) has been used as a pharmacologic strategy when the blunted response of endogenous erythropoietin has been reported in critically-ill people. The use of ESAs becomes more important where adverse clinical outcomes of transfusing blood products is a limitation. However, this indication for ESAs is not licensed by regulatory authorities and is called off-label use. Recent studies concern the harm of ESAs in a critical care setting. To focus on harms in assessing the effects of erythropoiesis-stimulating agents (ESAs), alone or in combination, compared with placebo, no treatment or a different active treatment regimen when administered off-label to critically-ill people. We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO via OvidSP, CINAHL, all evidence-based medicine (EBM) reviews including IPA and SCI-Expanded, Conference Proceedings Citation Index- Science, BIOSIS Previews and TOXLINE up to February 2017. We also searched trials registries, checked reference lists of relevant studies and tracked their citations by using SciVerse Scopus. We considered randomized controlled trials (RCTs) and controlled observational studies, which compared scheduled systemic administration of ESAs versus other effective interventions, placebo or no treatment in critically-ill people. Two review authors independently screened and evaluated the eligibility of retrieved records, extracted data and assessed the risks of bias and quality of the included studies. We resolved differences in opinion by consensus or by involving a third review author. We assessed the evidence using GRADE and created a 'Summary of findings' table. We used fixed-effect or random-effects models, depending on the heterogeneity between studies. We fitted three-level hierarchical Bayesian models to calculate overall treatment effect estimates. Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design.It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence).There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence). Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 262 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 262 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 39 15%
Student > Bachelor 32 12%
Researcher 27 10%
Other 16 6%
Student > Ph. D. Student 13 5%
Other 36 14%
Unknown 99 38%
Readers by discipline Count As %
Medicine and Dentistry 77 29%
Nursing and Health Professions 31 12%
Pharmacology, Toxicology and Pharmaceutical Science 8 3%
Social Sciences 7 3%
Psychology 6 2%
Other 31 12%
Unknown 102 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 20 March 2018.
All research outputs
of 22,999,744 outputs
Outputs from Cochrane database of systematic reviews
of 12,348 outputs
Outputs of similar age
of 316,647 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 275 outputs
Altmetric has tracked 22,999,744 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,348 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 30.7. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
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 316,647 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 275 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.