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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Interventions provided in the acute phase for mild traumatic brain injury: a systematic review

J Gravel, A D'Angelo, B Carriere, L Crevier, MH Beauchamp, JM Chauny, M Wassef, and N Chaillet.

Review published: 2013.

Link to full article: [PMC free article: PMC3750385]

CRD summary

This review concluded that there was a paucity of well-designed clinical trials for patients who sustain mild traumatic brain injury. The large variability in outcomes measured in the included trials limited comparison between them. This was a well-conducted review and the authors' conclusion seems appropriate and reliable.

Authors' objectives

To evaluate interventions that could be initiated in an acute setting for patients who sustain a mild traumatic brain injury.


PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), EBM Reviews, and ACP Journal Club were searched with no language restrictions from 1980 up to August 2012; search terms were reported. Conference proceedings from 2010, 2011, and 2012 of five relevant societies and Google Scholar were also searched, along with references from relevant reviews and clinical trials.

Study selection

Randomised controlled trials (RCTs) and clinical trials that evaluated any intervention initiated in an acute setting versus any comparator or placebo for patients experiencing acute mild traumatic brain injury (defined as a Glasgow coma score between 13 and 15 and one of four listed symptoms) were eligible for inclusion. Inclusion was not restricted by outcomes or participant age. Trials were excluded if the time between the trauma and the intervention was more than one week or only subgroups of patients were recruited.

Most of the participants were adolescents or adults. Most of the included trials reported assessments of post-concussion symptoms as the primary outcome measured more than two months after the intervention. Trials used different measurement tools for the same outcomes. Across the trials, the age of participants ranged from 6 months 65 years.

Three reviewers independently screened titles and abstracts. Two reviewers independently applied the inclusion criteria to full papers. Disagreements were resolved by discussion or referral to a third reviewer.

Assessment of study quality

Two reviewers independently assessed trial quality using the criteria of the Cochrane Effective Practice and Organization of Care review group. These included proper randomisation procedure, objective measurement of performance, and relevant and interpretable data. Disagreements were resolved by discussion.

Data extraction

Two reviewers independently extracted data to calculate risk ratios with 95% confidence intervals. Authors were contacted for missing data.

Methods of synthesis

A meta-analysis was conducted if two or more trials evaluated a similar intervention, and measured the same outcome during the same time frame. Pooled odds ratios (Peto OR if the number of events in a group was equal to 0) with 95% confidence intervals were calculated using a DerSimonian and Laird random-effects model. Heterogeneity was investigated using Cochran Q and Ι²; where Ι² was below 50%, a fixed-effect model was used. Where significant heterogeneity was detected, subgroup analyses were conducted by type of study intervention.

Where meta-analyses could not be performed due to substantial heterogeneity, a narrative synthesis was presented.

Results of the review

Fifteen RCTs met the inclusion criteria (7,275 participants, range 17 to 2,602). Five trials were considered to be at a high risk of bias, and six an unclear risk of bias. Randomisation generation and allocation concealment were the main areas of limitation.

Different follow-up interventions (seven trials): Compared with routine or no follow-up, a follow-up intervention had a positive effect in three studies using a telephone call and information booklets, with (two trials) or without (one trial) follow-up in a specialized clinic five to seven days after the trauma. Meta-analyses of four trials showed no significant benefit of a follow-up intervention for headache, concentration, memory, dizziness, vision, fatigue, irritability, anxiety, depression, or sensitivity to noise. Results of subgroup analyses were reported.

Information interventions (four trials): Three trials reported no benefit compared to usual care in decreasing post-concussion symptoms, while one trial reported that meeting with a specialized therapist and the provision of a 10-page information booklet decreased post-concussion symptoms. One trial suggested that standardized information and reassurance provided at the emergency department was associated with faster return to work and social activities. Overall, there was no association between the intervention and the persistence of headache (RR 0.88, 95% CI 0.65 to 1.19) or vision impairment (RR 0.58, 95% CI 0.10 to 3.31).

Compared with placebo (one trial with 17 adults), 10μg twice daily of nasal 1-desamino-8-d-arginine-vasopressin administered for five days was associated with better performance on two memory tests on the third day of treatment (data not provided); the intervention had no influence on four other cognitive outcomes.

Neither full bed rest (one trial) nor admission (one trial) showed a significant clinical benefit between two weeks to six months.

Immediate head computed tomography showed no significant difference at six months when compared to admission (one trial).

Authors' conclusions

There was a paucity of well-designed clinical trials for patients who sustained mild traumatic brain injury. The large variability in outcomes measured in trials limited comparison between them.

CRD commentary

The review addressed a clear question supported by reproducible inclusion criteria. The search was comprehensive, including sources for published and unpublished studies, and no language restrictions. Each stage of the review was conducted in duplicate, which reduced the risk of reviewer error and bias.

Appropriate criteria were used to assess trial quality, with the risk of bias and methodological limitations presented for each trial. The methods of synthesis seem appropriate.

This was a generally well-conducted review and the conclusion and recommendations for research seem appropriate and reliable.

Implications of the review for practice and research

Practice: The authors did not state implications for practice.

Research: The authors stated that a rigorous evaluation of the mid-term and long-term effects of pharmacological interventions on decreasing acute symptoms of mild traumatic brain injury was needed. The authors also stated that although a composite index score comprising many symptoms secondary to mild traumatic brain injury may be more useful for research purposes, researchers should also collect data on individual symptoms to permit comparison of studies. Researchers should measure outcomes at one week, one month and three months after trauma. Establishing what outcomes would be meaningful to patients with mild traumatic brain injury could also be useful.


Fonds de Recherche du Quebec-Sante (FRQ-S).

Bibliographic details

Gravel J, D'Angelo A, Carriere B, Crevier L, Beauchamp MH, Chauny JM, Wassef M, Chaillet N. Interventions provided in the acute phase for mild traumatic brain injury: a systematic review. Systematic Reviews 2013; 2:63. [PMC free article: PMC3750385] [PubMed: 23924958]

Indexing Status

Subject indexing assigned by CRD


Brain Concussion /therapy; Humans



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 23924958