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Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

Overview of attention for article published in Cochrane database of systematic reviews, November 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • Average Attention Score compared to outputs of the same age and source

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16 tweeters

Citations

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9 Dimensions

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114 Mendeley
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Title
Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia
Published in
Cochrane database of systematic reviews, November 2017
DOI 10.1002/14651858.cd008727.pub4
Pubmed ID
Authors

Niki Rensen, Reinoud JBJ Gemke, Elvira C van Dalen, Joost Rotteveel, Gertjan JL Kaspers

Abstract

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infection, which remain a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear. This review is the second update of a previously published Cochrane review. To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), MEDLINE/PubMed (from 1945 to December 2016), and Embase/Ovid (from 1980 to December 2016). In addition, we searched reference lists of relevant articles, conference proceedings (the International Society for Paediatric Oncology and the American Society of Clinical Oncology from 2005 up to and including 2016, and the American Society of Pediatric Hematology/Oncology from 2014 up to and including 2016), and ongoing trial databases (the International Standard Registered Clinical/Social Study Number (ISRCTN) register via http://www.controlled-trials.com, the National Institutes of Health (NIH) register via www.clinicaltrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (WHO) via apps.who.int/trialsearch) on 27 December 2016. All study designs, except case reports and patient series with fewer than 10 children, examining effects of glucocorticoid therapy for childhood ALL on HPA axis function. Two review authors independently performed study selection. One review author extracted data and assessed 'Risk of bias'; another review author checked this information. We identified 10 studies (total of 298 children; we identified two studies for this update) including two randomised controlled trials (RCTs) that assessed adrenal function. None of the included studies assessed the HPA axis at the level of the hypothalamus, the pituitary, or both. Owing to substantial differences between studies, we could not pool results. All studies had risk of bias issues. Included studies demonstrated that adrenal insufficiency occurs in nearly all children during the first days after cessation of glucocorticoid treatment for childhood ALL. Most children recovered within a few weeks, but a small number of children had ongoing adrenal insufficiency lasting up to 34 weeks.Included studies evaluated several risk factors for (prolonged) adrenal insufficiency. First, three studies including two RCTs investigated the difference between prednisone and dexamethasone in terms of occurrence and duration of adrenal insufficiency. The RCTs found no differences between prednisone and dexamethasone arms. In the other (observational) study, children who received prednisone recovered earlier than children who received dexamethasone. Second, treatment with fluconazole appeared to prolong the duration of adrenal insufficiency, which was evaluated in two studies. One of these studies reported that the effect was present only when children received fluconazole at a dose higher than 10 mg/kg/d. Finally, two studies evaluated the presence of infection, stress episodes, or both, as a risk factor for adrenal insufficiency. In one of these studies (an RCT), trial authors found no relationship between the presence of infection/stress and adrenal insufficiency. The other study found that increased infection was associated with prolonged duration of adrenal insufficiency. We concluded that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. No data were available on the levels of the hypothalamus and the pituitary; therefore, we could draw no conclusions regarding these outcomes. Clinicians may consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL to reduce the risk of life-threatening complications. However, additional high-quality research is needed to inform evidence-based guidelines for glucocorticoid replacement therapy.Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as these treatments may prolong the duration of adrenal insufficiency, especially when administered at a dose higher than 10 mg/kg/d.Finally, it would be relevant to investigate further the relationship between present infection/stress and adrenal insufficiency in a larger, separate study specially designed for this purpose.

Twitter Demographics

The data shown below were collected from the profiles of 16 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 114 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 <1%
Italy 1 <1%
United Kingdom 1 <1%
Mexico 1 <1%
Denmark 1 <1%
Unknown 109 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 18%
Researcher 16 14%
Student > Bachelor 16 14%
Student > Master 14 12%
Unspecified 10 9%
Other 36 32%
Unknown 1 <1%
Readers by discipline Count As %
Medicine and Dentistry 63 55%
Unspecified 15 13%
Psychology 8 7%
Nursing and Health Professions 4 4%
Agricultural and Biological Sciences 4 4%
Other 19 17%
Unknown 1 <1%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 25 January 2018.
All research outputs
#1,961,684
of 13,190,464 outputs
Outputs from Cochrane database of systematic reviews
#4,670
of 10,519 outputs
Outputs of similar age
#65,164
of 311,948 outputs
Outputs of similar age from Cochrane database of systematic reviews
#142
of 256 outputs
Altmetric has tracked 13,190,464 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,519 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.6. This one has gotten more attention than average, scoring higher than 55% 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 311,948 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 79% of its contemporaries.
We're also able to compare this research output to 256 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.