0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letter |

A Living Systematic Review of Nebulized Hypertonic Saline for Acute Bronchiolitis in Infants FREE

Robert G. Badgett, MD1,2; Mohinder Vindhyal, MD1,3; Jason T. Stirnaman, MLS4; C. Michael Gibson, MD5; Rim Halaby, MD5
[+] Author Affiliations
1Department of Internal Medicine, Kansas University School of Medicine, Wichita
2Department of Preventive Medicine and Public Health, Kansas University School of Medicine, Wichita
3Department of Pediatrics, Kansas University School of Medicine, Wichita
4A. R. Dykes Library, Kansas University School of Medicine, Wichita
5PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
JAMA Pediatr. 2015;169(8):788-789. doi:10.1001/jamapediatrics.2015.0681.
Text Size: A A A
Published online

Grewal and Klassen1 in JAMA Pediatrics note the frustrations in interpreting evidence about bronchiolitis. Evidence is spread across a prior meta-analysis and other trials. The Grewal and Klassen editorial1 encourages living systematic reviews that are updated as new trials emerge. We use the topic of nebulized hypertonic saline for bronchiolitis to propose the method of a living systematic review.

METHODS

In this meta-analysis, we started by including the same trials in the Cochrane review by Zhang et al.2 We then searched for newer trials in the Cochrane Central Register of Controlled Trials and articles in Web of Science that cited the Zhang et al study.2 Our methods are detailed online at the living review (http://openmetaanalysis.github.io/Hypertonic-Saline-for-Bronchiolitis/).

RESULTS

We identified 11 new trials (4 only available at http://clinicaltrials.gov).1 The meta-analysis showed that hypertonic saline significantly reduced the length of stay (LOS) among hospitalized infants. Heterogeneity was largely owing to variation in LOS in the control groups of trials. Benefit was confined to studies with a long LOS; however, even within this group study, results of recent trials were negative. Among infants given multiple doses, symptoms were improved and hospitalization was reduced. Forest plots, meta-regressions, and risk of bias assessment are available online. Quality of evidence as assessed by the GRADEprofiler was low owing to imprecision and other factors detailed in the GRADEprofiler online.

DISCUSSION

Prior research was comprehensively summarized by the Cochrane review. The addition of the newer trials attenuated the results of all outcomes. However, all outcomes were statistically significant owing to reduction in hospitalization in the subgroup analysis of infants who received multiple doses of treatment. The reduction in LOS was confined to older trials with a longer LOS. We rated the quality of evidence lower than the Cochrane review. This is likely owing to downgrading evidence according to criteria listed in our summary of findings table and methods (http://openmetaanalysis.github.io/Hypertonic-Saline-for-Bronchiolitis/). The small number of patients studied limit both generalizability and the certainty of conclusions.

This topic validates the Grewal and Klassen1 recommendation for living systematic reviews. Further, a practice guideline3 and meta-analysis4 on the same topic were published this year and neither included the newer trials. Living reviews provide opportunities (Box) to advance knowledge creation, discourage unnecessary trials, and prevent under-recognition of prior research by trialists5 and authors.6 In addition, living reviews may help medical education via experiential learning (Box).

Box Section Ref ID

Box.
Living Systematic Review Opportunities
Knowledge Creation
  • Living reviews may accompany requests for funding or ethics approval to justify proposed research.

  • Living reviews may accompany manuscripts during peer review to place research in context.

  • Living reviews can be done by nontrialists when a trial that is not accompanied by a systematic review is published and affects a body of evidence.

  • Living reviews may encourage collaboration by reducing barriers to contributions by individuals.

Medical Education
  • Living reviews or updates to reviews that consist of a few trials may be authored by supervised trainees.

  • Living reviews may help teach numeracy by assessing the change in outcomes and heterogeneity after adding new studies.

  • Living reviews may teach epistemological concepts if the methods of GRADE and QUADAS-2 are used.

  • Living reviews may provide up-to-date content for tertiary educational publications, such as wikis. This is supported by GNU General Public Licensing.

Repositories of living systematic reviews may be hosted at GitHub (http://openmetaanalysis.github.io/), as we did, or at the Systematic Review Data Repository (http://srdr.ahrq.gov/). GitHub provides web hosting and sharing repositories with version control. In addition, it offers wikis, issue tracking, communication, and social networking features that facilitate rapid collaborative knowledge work. Beyond sharing code, GitHub now hosts projects ranging from simple documents to complex governmental legislation.

Methods for living systematic reviews will evolve both technically and procedurally. For example, should open repositories include exhaustive interpretations of data? We propose that repositories should focus on the data and then link to interpretations of data in journals or tertiary publications, such as online textbooks and wikis. How can living reviews be designed to complement rather than compete with exhaustive reviews published by Cochrane and others? One solution is that when the published review is current, the living review will indicate there are no recent trials and link to the exhaustive review.

Available evidence, although low quality, suggests that hypertonic saline for bronchiolitis decreases the LOS for hospitalized children and may reduce symptoms and the rate of hospitalization. We encourage colleagues to help maintain this review, create other reviews, and advance the methods of living systematic reviews. Analyses and figures will be updated at http://openmetaanalysis.github.io/Hypertonic-Saline-for-Bronchiolitis/ as new trials are published.

ARTICLE INFORMATION

Corresponding Author: Robert G. Badgett, MD, Departments of Internal Medicine, Preventive Medicine, and Public Health, Kansas University School of Medicine, 1010 N Kansas St, Wichita, KS 67214-3199 (rbadgett@kumc.edu).

Published Online: June 22, 2015. doi:10.1001/jamapediatrics.2015.0681.

Author Contributions: Dr Badgett had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Badgett, Stirnaman.

Acquisition, analysis, or interpretation of data: Badgett, Vindhyal, Gibson, Halaby.

Drafting of the manuscript: Badgett, Vindhyal, Stirnaman.

Critical revision of the manuscript for important intellectual content: Badgett, Stirnaman, Gibson, Halaby.

Statistical analysis: Badgett, Vindhyal, Gibson.

Administrative, technical, or material support: Badgett, Vindhyal, Stirnaman.

Study supervision: Badgett.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We acknowledge the patient assistance provided directly and indirectly by Jeroen Ooms, PhD, Department of Statistics, University of California Los Angeles, creator of https://www.opencpu.org/, and Guido Schwarzer, PhD, Institute for Medical Biometry and Statistics, Medical Center; University of Freiburg, Germany, author of http://cran.r-project.org/web/packages/meta/. Neither individual received financial compensation.

REFERENCES

Grewal  S, Klassen  TP.  The tale of 2 trials: disentangling contradictory evidence on hypertonic saline for acute bronchiolitis. JAMA Pediatr. 2014;168(7):607-609.
PubMed   |  Link to Article
Zhang  L, Mendoza-Sassi  RA, Wainwright  C, Klassen  TP.  Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2013;7:CD006458.
PubMed
Ralston  SL, Lieberthal  AS, Meissner  HC,  et al; American Academy of Pediatrics.  Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474-e1502.
PubMed   |  Link to Article
Chen  YJ, Lee  WL, Wang  CM, Chou  HH.  Nebulized hypertonic saline treatment reduces both rate and duration of hospitalization for acute bronchiolitis in infants: an updated meta-analysis. Pediatr Neonatol. 2014;55(6):431-438.
PubMed   |  Link to Article
Cooper  NJ, Jones  DR, Sutton  AJ.  The use of systematic reviews when designing studies. Clin Trials. 2005;2(3):260-264.
PubMed   |  Link to Article
Robinson  KA, Goodman  SN.  A systematic examination of the citation of prior research in reports of randomized, controlled trials. Ann Intern Med. 2011;154(1):50-55.
PubMed   |  Link to Article

Figures

Tables

References

Grewal  S, Klassen  TP.  The tale of 2 trials: disentangling contradictory evidence on hypertonic saline for acute bronchiolitis. JAMA Pediatr. 2014;168(7):607-609.
PubMed   |  Link to Article
Zhang  L, Mendoza-Sassi  RA, Wainwright  C, Klassen  TP.  Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2013;7:CD006458.
PubMed
Ralston  SL, Lieberthal  AS, Meissner  HC,  et al; American Academy of Pediatrics.  Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474-e1502.
PubMed   |  Link to Article
Chen  YJ, Lee  WL, Wang  CM, Chou  HH.  Nebulized hypertonic saline treatment reduces both rate and duration of hospitalization for acute bronchiolitis in infants: an updated meta-analysis. Pediatr Neonatol. 2014;55(6):431-438.
PubMed   |  Link to Article
Cooper  NJ, Jones  DR, Sutton  AJ.  The use of systematic reviews when designing studies. Clin Trials. 2005;2(3):260-264.
PubMed   |  Link to Article
Robinson  KA, Goodman  SN.  A systematic examination of the citation of prior research in reports of randomized, controlled trials. Ann Intern Med. 2011;154(1):50-55.
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

2,010 Views
7 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Meta-analysis

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence Summary and Review