PONE-D-24-50934Traumatic Brain Injury in Ethiopia, A Systematic Review and Meta-analysisPLOS ONE

Dear Dr. Molla,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

See reviewer comments below.

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We look forward to receiving your revised manuscript.

Kind regards,

Alvan-Emeka K. Ukachukwu, MD, MSc.GH

Academic Editor

PLOS ONE

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Additional Editor Comments:

The manuscript requires significant revisions as noted by the reviewers. Kindly provide detailed responses to the reviewer comments.

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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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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:  1. Please include more info regarding your strategy to collect the demographics and do the meta-analysis specifically in Ethiopia, which will be useful to anyone who is s a foreigner to the policies and census in Ethiopia. There was no details regarding how to you were able confirm these numbers. Resources and reference for confirmation would have been very helpful. I understand you included references "at times", but why do you pick these studies, would have been a very helpful input.

2. Rewrite the demographics section. For example, stating that males are 78, females are 22% is redundant. A more useful piece of info is how these populations in the different studies differed in every study when compared to the whole and why.

3. Please summarize the confidence intervals. I prefer this info to be in a table, for comparison. At times, it was wordy and not helpful.

4. Better describe figures. e.g. Figure 2: Forest plot of assault/violence as a cause of TBI in Ethiopia this should have been Figure 2: assault/violence as a cause of TBI in Ethiopia. Above is a Forest plot describing so and so.

5. I would suggest changing the name of the study e.g. "the prevalence of TBI in Ethiopia" or " comparing TBI prevalence in Ethiopia to the rest of sub-Saharan Africa", "The mechanism of TBI in Ethiopia" or whatever the authors prefer.

6. There was no in depth analysis for the data in the supplementary material when it relates in Ethiopia, but only a referral to why the numbers are low in other countries per their reference.

7. the JIB approach and grade tables were great efforts, and referring to them is helpful but should have better suited in the supplementary material, as they are not the focus of this study, and rather bring more info from the supplementary to the main other the mere causes and mortality rate. Still can be included in a paragraph and two as a summary.

Reviewer #2:  This manuscript presents a systematic review and meta-analysis on traumatic brain injury (TBI) in Ethiopia. The study addresses a significant public health issue, given the high prevalence and associated challenges of TBI globally, especially in regions with limited healthcare resources like Ethiopia.

Strengths

Rigorous Research Methodology

The study strictly adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From the comprehensive literature search across multiple databases (PubMed, Scopus, Web of Science, and EMBASE) using well-defined search terms and strategies, to the meticulous data extraction and quality assessment process, every step is methodologically sound. The employment of the Joanna Briggs Institute (JBI) critical appraisal checklist and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for evaluating study quality and evidence certainty further enhances the scientific rigor. The use of Stata 17 software and random-effects models to handle heterogeneity and assess publication bias is also appropriate and adds to the reliability of the findings.

Comprehensive Data Collection

The authors' efforts in conducting a thorough literature search, including both electronic database searches and manual reviews of reference lists, ensure a wide coverage of relevant studies. This comprehensive approach maximizes the likelihood of capturing all available evidence related to TBI in Ethiopia, strengthening the foundation of the analysis.

Weaknesses and Suggestions

Sample Representativeness Issue

The studies included in the review are disproportionately concentrated in certain regions, such as Addis Ababa. This uneven distribution may lead to a biased estimation of the national TBI burden, as rural and underserved areas might have different TBI patterns and risk factors. To address this, future research should prioritize large-scale, nationally representative studies. This could involve stratified sampling techniques to ensure adequate representation from all regions, including those that are currently under-researched. Additionally, collaborating with local healthcare providers and community organizations in different areas can facilitate data collection and improve the comprehensiveness of the sample.

Publication Bias Concern

By relying solely on published studies, the meta-analysis is susceptible to publication bias. Studies with significant results are more likely to be published, potentially skewing the overall picture. To mitigate this, the authors could consider exploring unpublished studies, such as those presented in conference proceedings or registered in trial databases. Grey literature searches can also be incorporated to capture a more complete range of research findings. This would provide a more balanced and accurate assessment of the TBI situation in Ethiopia.

Diagnostic Limitations

Many of the included studies lack access to advanced imaging modalities like CT or MRI, particularly in rural settings. This deficiency may result in the underreporting of TBI severity and complexity, as milder cases or subtle brain injuries could go undetected. Future investigations should aim to improve diagnostic capabilities in these areas. This could involve providing training and resources for healthcare workers to better identify and document TBI cases. Mobile diagnostic units equipped with appropriate imaging technology could also be deployed to reach rural and remote areas, ensuring more accurate diagnosis and a more comprehensive understanding of the true prevalence and nature of TBI.

Variability in Trauma Care Consideration

The variability in trauma care availability across Ethiopia is not adequately accounted for in the current analysis. Different levels of healthcare infrastructure and resources can significantly impact patient outcomes, including mortality and complication rates. To rectify this, future studies should incorporate trauma care availability as a variable in the analysis. This could involve collecting data on factors such as the number of trained healthcare providers, availability of critical care facilities, and access to emergency medical services in different regions. By adjusting for these factors, a more accurate assessment of the impact of TBI and the effectiveness of interventions can be achieved.

Reviewer #3:  The manuscript by Yohannis Derbew Molla and Hirut Tesfahun Alemu provides an essential and timely systematic review and meta-analysis on the prevalence, causes, and outcomes of TBI in Ethiopia. The study addresses a significant public health concern and highlights critical gaps in trauma care and prevention in a low-resource setting. The manuscript is well-organized and adheres to the PRISMA guidelines. However, several issues need to be addressed to enhance the clarity, accuracy, and impact of the study.

Major Comments

1. Authors acknowledge the data heterogeneity (e.g., I² values), they should explore subgroup analyses based on geographical regions, study design, or study population demographics to provide insights into the variability.

2. Include a funnel plot or Egger’s test results in the manuscript to substantiate the claim of publication bias assessment.

3. Clarify how mortality rates and complications were standardized across studies. Were these definitions uniform across studies, or did variability exist?

4. The lack of representation from certain Ethiopian regions, particularly rural and underserved areas, is a limitation. Highlight how this could impact the generalizability of findings.

5. Expand on the implications for Ethiopian health policy and trauma care systems. For example, how might these findings inform resource allocation or prevention strategies for road traffic accidents and violence?

Minor Comments

1. Rephrase ambiguous sentences for clarity, e.g., “... insufficient healthcare infrastructure... exacerbated by limited access to specialized medical services” could be refined for readability.

2. Include exact sample sizes (n) for all pooled estimates in tables and figures legends.

3. Verify the inclusion of all mandatory PRISMA elements, particularly in the supplementary material.

4. Provide additional details on statistical corrections for heterogeneity, if any were used.

5. Ensure recent references are cited for comparisons with other LMICs or African nations.

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Reviewer #1: Yes:  Adel Elnashar

Reviewer #2: No

Reviewer #3: Yes:  Syed M. Faisal, Ph.D.

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PONE-D-24-50934R1Epidemiology of Traumatic Brain Injury in Ethiopia: A Systematic Review and Meta-Analysis of Prevalence, Mechanisms, and OutcomesPLOS ONE

Dear Dr. Molla,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: See reviewer comments below. ==============================

Please submit your revised manuscript by Apr 21 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Alvan-Emeka K. Ukachukwu, MD, MSc.GH

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Please address the outstanding comments by the reviewer.

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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: (No Response)

Reviewer #3: 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: No

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #3: Yes

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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 #3: 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 #3: Yes

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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: Thank you for your hard work reviewing the comments and rewriting. The quality of the work has much improved.

-Remove all forest plots and in a simple table list all the heterogeneity results for the different variables in question. The plot shows the heterogeneity, but in themselves don’t add much information, can be included in supplementary.

-in introduction, there is a consistent jump back and forth to the prevalence of TBI and the impact of TBI.

- The variable inconsistency between retrospective asnd prospective studies doesn’t indicate that what you mentioned. These variables are indeed expected to produce this effect, but your mentioned conclusion can’t be deducted from this input, unless the prospective studies shared population, methodology..etc. is this the case? include then.

-Having your own mortality rate definition is confusing, provide a different term.

-Your study has significant inconsistency, I2, this should your number one limitation, and the first recommendations should address this subject. Your discussion should also include it in your first to second paragraph as it reflects on all your input and conclusions.

-The paragraph with the heterogeneity and the publication bias, include each separately, they are unrelated, only include the numbers under results, and include your suggestions and reflections under discussions.

-Egger test coding can also be included under supplementary.

-Surgical intervention doesn’t reflect severity, indeed many of the most severe TBI aren’t warranted for surgery.Surgery is a tool used when it is indicated.A slight midline shift may indicate a surgery need, but a more severe bleed, may not benefit from surgery.

-Don’t use GCS to classify TBI severity in your study unless isolated, GCS can vary depending on general state, or otherwise list GCS ranges without referring to TBI severity.

-There was multiple outcomes variable added in your new manuscript. There was multiple versions, but after adding this, there was no consistency in using it elements for analysis. Please review these outcomes or remove.

Reviewer #3: The authors have adequately addressed and incorporated the requested information in the revised version of the manuscript.

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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: Yes:  Adel Elnashar

Reviewer #3: Yes:  Syed M. Faisal

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Epidemiology of Traumatic Brain Injury in Ethiopia: A Systematic Review and Meta-Analysis of Prevalence, Mechanisms, and Outcomes

PONE-D-24-50934R2

Dear Dr. Yohannis Molla,

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.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Alvan-Emeka K. Ukachukwu, MD, MSc.GH

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

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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

**********

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

Reviewer #1: 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

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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

**********

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: Thank you for addressing my latest comments. Good luck!

I think a small map of Ethiopia would have been helpful to familiarize the reader with the geographical context of your work, especially if you are addressing an international audience. This won’t impact the core of the work or conclusion. Interested readers can seek a map on their own time. You have a couple of sentences that were redundant, but they are acceptable.

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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: Yes:  Adel Elnashar

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