PONE-D-20-28037

Blue-wavelength light therapy for post-traumatic brain injury sleepiness, sleep disturbance, depression, and fatigue: a systematic review and network meta-analysis

PLOS ONE

Dear Dr. Srisurapanont,

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Based on the comments of the reviewers, we feel a minor revision would be appropriate.

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Sahil Bajaj, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Thank you for the opportunity to review this manuscript. I do apologize for the delay in getting this review done. I know how frustrating it can be to sit and wait for reviewers to finish.

Developing and identify safe and efficacious TBI treatments is a growing public goal that is understandably burdened by generally small sample sizes in individual trials. To this end, systematic reviews/meta-analyses of this nature are essential to understanding the broader landscape of the literature.

Overall, I found this meta-analysis to be clearly written with clear methodology and interpretations that appropriately reflected the conducted analyses. However, I do have one concern that I did not find addressed anywhere in the manuscript. The four reviewed RCTs were conducted on very diverse populations. While all of the trials were on the TBI spectrum, Killgore and Raikes were exclusively on mTBI, while Sinclair was conducted on mixed severity and Quera Salva on severe. Additionally, treatment timings were very different across studies, with Killgore and Raikes being the most similar.

There is no indication that any of the analyses accounted for these very key differences. The longitudinal outcomes from severe TBI are very different from those for mild TBI/concussion. The recovery time curves are very different across these injury types as well. Particularly for a study like Quera Salva et al. where the average post-injury timing was 9 years compared to Raikes et al at 6 months, it's unclear how treatment timing and injury severity may play a role in these outcomes.

Please either clarify or revise this manuscript to address this concern. I recognize that there are only 4 studies to draw from and statistical methods are likely insufficient to tease apart these effects. The discussion should, at a minimum, present some interpretation/context for these issues.

Once again, thank you for the opportunity to read this manuscript. I look forward to the revised version.

Reviewer #2: I was delighted to review the manuscript. It addresses an interesting major topic (i.e. post-traumatic brain injury sleepiness, sleep disturbance, depression, and fatigue, and the efficacy of blue-wavelenght light therapy). The authors performed in a comprehensive methodologically way this systematic review and meta-analyses. The manuscript is nicely written and the results and discussion are coherent with the methodology. However, two minor issues need to be improved.

1. Introduction: First sentence ‘Post-TBI depression, fatigue, and sleepiness are…’ (page 3, line 66-67) and third sentence ‘These three symptoms are similar to…’ (page 3, line 68-69), could be rephrased to avoid repetition.

2. Information sources: ‘from their inceptions’ (page 6, line 133-134) it is better to include the date of the last search (e.g., from their inceptions to July 4th 2020).

Best wishes.

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Reviewer #1: No

Reviewer #2: No

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Blue-wavelength light therapy for post-traumatic brain injury sleepiness, sleep disturbance, depression, and fatigue: a systematic review and network meta-analysis

PONE-D-20-28037R1

Dear Dr. Srisurapanont,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Sahil Bajaj, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: