PONE-D-20-33033

Posterior Circulation Acute Stroke Prognosis Early CT Scores in Predicting Functional Outcomes: A Meta-analysis

PLOS ONE

Dear Dr. Lin,

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Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This article innovates as it aims to establish if PC-ASPECTS may predict functional outcomes in patients with acute ischemic stroke. This has been an issue with NIHSS and ASPECTS as both scales are focused in anterior circulation strokes. The authors followed a systematic review (SR) approach for searching available articles with a meta-analyses (MA) that used a random effects modeling approach to account for heterogeneity. Even though the main objectives of this research were achieved, the presentation of results fails to be clear to the reader at several points of the article and this should be addressed prior to the approval for publication of this article.

1. The authors do not establish if their SR was previously registered at PROSPERO registry. Currently this is highly expected when attempting a SR in order to later compare the results obtained and the methodological approach performed with the protocol published at the beginning of the investigation. I did a search in the PROSPERO registry and could not find this SR registered, I would like to ask the authors if their review was previously registered and if they followed a previously determined protocol for this.

2. The authors confuse along the whole article between subgroups and sensitivity analysis in regards of their comparison of the results between patients with and without Intra-arterial endovascular treatment (IA-EVT). This by no means should be considered a sensitivity analysis, specially if you are reporting different outcomes obtained after a different intervention was applied. This should be formally analyzed and described as subgroup analysis. On the contrary, evaluating the differential effect of CT/MRI and different definitions of UFO based on mRS, could be better considered as sensitivity analysis as they would be assessing the same outcome but defined differently, yet not assessing the effect of different interventions. I highly recommend the authors to thoroughly review Cochrane Handbook of Systematic Reviews Chapter 10 to understand better the distinction between sensitivity and subgroup analysis, as both terms are commonly confused.

3. In similar terms, the results section should fully describe the results of sensitivity analysis. This was not described in any detail, yet it was referred to in the discussion part under "Studies with varied definitions of UFO and imaging modalities".

4. As I read the article, it becomes very confusing the cut-offs used by the authors for PC-ASPECTS that determined the best effect. In the discussion they chose 7-8 as the best cut-off but there should be more emphasis along the paper, as they describe the results of their analysis, in regards of what cut-offs should be taken as the main predictors, and specifying the effects sizes that lead into determining what cut-offs are best.

5. Some other minor changes that should be made:

- when describing the analysis of only 1 article, reporting 0.0% of heterogeneity (I2) is redundant and misleading. It is rather obvious that one article will not be heterogeneous on its own.

- it would be good for the reader to describe the authors cut-off points for heterogeneity, otherwise their interpretation of the I2 values seem rather arbitrary. I recommend Chapter 10 of Cochran SR Handbook where they establish cute-offs for heterogeneity.

- Please correct every time you refer to this search as "systemic search". This terminology is incorrect and should be "systematic research".

-Last paragraph of the discussion states "However, publication bias was excluded in our analyses". This is a daring phrase as funnel plots cannot fully exclude publication bias, please rephrase this sentence accordingly.

- It is highly expected in the PRISMA chart that the authors specify the reasons that made them exclude papers. Please list reasons for exclusion.

- Finally, I saw that the supplementary tables have a review of quality of the data retrieved yet there is no description of this in the results or discussion. I would like to know as a reader the quality of the data retrieved.

Reviewer #2: This is a very precise, informative and well written article. The predictive value of PC- ASPECTS is a very pertinent subject since the posterior circulation stroke are usually overlooked in the major trials.

I only have one question for the authors. Regarding the following statement

Furthermore, for patients treated with IA-EVT, sensitivity analyses only indicated a robust association between UFO prediction and PC-ASPECTS.

Why do you think there was only robust association between UFO and PC- ASPECTS when treated with AI EVT? Do you think this is due to the heterogenicity of the IA – EVT studies or perhaps that the therapy itself may modify the outcomes.

This is a high quality and pertinent paper; therefore, I recommend its publication.

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Reviewer #1: No

Reviewer #2: Yes: Beatriz Mendez

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Posterior Circulation Acute Stroke Prognosis Early CT Scores in Predicting Functional Outcomes: A Meta-analysis

PONE-D-20-33033R1

Dear Dr. Lin,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors fully addressed all my concerns and the current manuscript reads better. They were able to describe better the statistic approach that led to their conclusions. To my appraisal this article is more understandable now as it was before, for the common reader that might not now about systematic reviews.

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Beatriz Mendez Gonzalez