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Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis

Overview of attention for article published in Cochrane database of systematic reviews, January 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 (75th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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4 tweeters
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1 Facebook page
wikipedia
1 Wikipedia page

Citations

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18 Dimensions

Readers on

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163 Mendeley
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Title
Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis
Published in
Cochrane database of systematic reviews, January 2017
DOI 10.1002/14651858.cd012040.pub2
Pubmed ID
Authors

Aisha A Aslam, Colin Higgins, Ian P Sinha, Kevin W Southern

Abstract

Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance. The resulting thick mucus makes the airway prone to chronic infection and inflammation, which consequently damages the structure of the airways, eventually leading to respiratory failure. Additionally, abnormalities in the cystic fibrosis transmembrane conductance regulator protein lead to other systemic complications including malnutrition, diabetes and subfertility.Five classes of mutation have been described, depending on the impact of the mutation on the processing of the cystic fibrosis transmembrane conductance regulator protein in the cell. In class I mutations, the presence of premature termination codons prevents the production of any functional protein resulting in a severe cystic fibrosis phenotype. Advances in the understanding of the molecular genetics of cystic fibrosis has led to the development of novel mutation-specific therapies. Therapies targeting class I mutations (premature termination codons) aim to mask the abnormal gene sequence and enable the normal cellular mechanism to read through the mutation, potentially restoring the production of the cystic fibrosis transmembrane conductance regulator protein. This could in turn make salt transport in the cells function more normally and may decrease the chronic infection and inflammation that characterises lung disease in people with cystic fibrosis. To evaluate the benefits and harms of ataluren and similar compounds on clinically important outcomes in people with cystic fibrosis with class I mutations (premature termination codons). We searched the Cochrane Cystic Fibrosis Trials Register which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles. Last search of Group's register: 24 October 2016.We searched clinical trial registries maintained by the European Medicines Agency, the US National Institutes of Health and the WHO. Last search of clinical trials registries: 28 November 2016. Randomised controlled trials of parallel design comparing ataluren and similar compounds (specific therapies for class I mutations) with placebo in people with cystic fibrosis who have at least one class I mutation. Cross-over trials were reviewed individually to evaluate whether data from the first treatment arm could be included. We excluded trials that combined therapies for premature termination codon class I mutations with other mutation-specific therapies. The authors independently assessed the risk of bias and extracted data from the included trial; they contacted trial authors for additional data. Our searches identified 28 references to eight trials; five trials were excluded (three were cross-over and one was not randomised and one did not have relevant outcomes), one cross-over trial is awaiting classification pending provision of data and one trial is ongoing. The included parallel randomised controlled trial compared ataluren to placebo for a duration of 48 weeks in 238 participants (age range 6 to 53 years) with cystic fibrosis who had at least one nonsense mutation (a type of class I mutation).The quality of evidence and risk of bias assessments for the trial were moderate overall. Random sequence generation, allocation concealment and blinding of trial personnel were well-documented; participant blinding was less clear. Some participant data were excluded from the analysis. The trial was assessed as high risk of bias for selective outcome reporting, especially when reporting on the trial's post hoc subgroup of participants by chronic inhaled antibiotic use.The trial was sponsored by PTC Therapeutics Incorporated with grant support by the Cystic Fibrosis Foundation, the Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health (NIH).The trial reported no significant difference between treatment groups in quality of life, assessed by the Cystic Fibrosis Questionnaire-Revised respiratory domain score and no improvement in respiratory function measures (mean difference of relative change in forced expiratory volume at one second 2.97% (95% confidence interval -0.58 to 6.52)). Ataluren was associated with a significantly higher rate of episodes of renal impairment, risk ratio 17.70 (99% confidence interval 1.28 to 244.40). The trial reported no significant treatment effect for ataluren for the review's secondary outcomes: pulmonary exacerbation; computerised tomography score; weight; body mass index; and sweat chloride. No deaths were reported in the trial.A post hoc subgroup analysis of participants not receiving chronic inhaled tobramycin (n = 146) demonstrated favourable results for ataluren (n = 72) for relative change in % predicted forced expiratory volume at one second and pulmonary exacerbation rate. Participants receiving chronic inhaled tobramycin appeared to have a reduced rate of pulmonary exacerbation compared to those not receiving chronic inhaled tobramycin. This drug interaction was not anticipated and may affect the interpretation of the trial results. There is currently insufficient evidence to determine the effect of ataluren as a therapy for people with cystic fibrosis with class I mutations. Future trials should carefully assess for adverse events, notably renal impairment and consider the possibility of drug interactions. Cross-over trials should be avoided given the potential for the treatment to change the natural history of cystic fibrosis.

Twitter Demographics

The data shown below were collected from the profiles of 4 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 163 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 163 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 36 22%
Student > Bachelor 24 15%
Student > Ph. D. Student 21 13%
Researcher 16 10%
Student > Postgraduate 8 5%
Other 26 16%
Unknown 32 20%
Readers by discipline Count As %
Medicine and Dentistry 56 34%
Nursing and Health Professions 18 11%
Psychology 11 7%
Pharmacology, Toxicology and Pharmaceutical Science 9 6%
Social Sciences 7 4%
Other 26 16%
Unknown 36 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 18 June 2017.
All research outputs
#2,738,897
of 12,527,219 outputs
Outputs from Cochrane database of systematic reviews
#5,117
of 8,923 outputs
Outputs of similar age
#83,027
of 337,676 outputs
Outputs of similar age from Cochrane database of systematic reviews
#113
of 189 outputs
Altmetric has tracked 12,527,219 research outputs across all sources so far. Compared to these this one has done well and is in the 78th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,923 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.2. This one has gotten more attention than average, scoring higher than 52% 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 337,676 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 75% of its contemporaries.
We're also able to compare this research output to 189 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.