Proportion of stroke types in Madagascar: A tertiary-level hospital-based case series

Julia Riedmann; Andriamihaja Flavien Solonavalona; Adriamboahanginiaina Ravosoa Rakotozafy; Solofo Ralamboson; Matthias Endres; Bob Siegerink; Eberhard Siebert; Samuel Knauss; Julius Valentin Emmrich

doi:10.1371/journal.pone.0276199

Peer Review History

Original SubmissionMay 10, 2022
7 Jul 2022 Decision Letter - Ismail Ibrahim Ismail, Editor PONE-D-22-13670Proportion of stroke types in Madagascar: a tertiary-level hospital-based case seriesPLOS ONE Dear Dr. Emmrich, 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. Please submit your revised manuscript by Aug 21 2022 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. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Thank you for stating the following in the Competing Interests section: "I have read the journal´s policy and the authors of this manuscript have the following competing interests: ME received funding from DFG under Germany's Excellence Strategy – EXC-2049 – 390688087, BMBF, DZNE, DZHK, EU, Corona Foundation, and Fondation Leducq. ME reports grants from Bayer and fees paid to Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, all outside the submitted work." Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. [Note: HTML markup is below. Please do not edit.] 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: No ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: No ****** 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: No ****** 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: No ****** 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: I do not think that this study represents the true stroke figures. The authors included patients with CT-confirmed stroke. A significant proportion of stroke patients would have a small infarction in MRI, which would not appear in CT. I think the authors should have included stroke patients meeting the old WHO definition of stroke, irrespective of the neuroimaging: acute-onset focal neurological deficits lasting more than 24hours. This would increase the proportion of ischemic stroke patients. Please consider adding this data to your study. Moreover, I think a significant proportion of stroke patients in SSA would not present to the hospital, which would explain the relatively higher prevalence of hemorrhagic stroke in this study. "Sub-Saharan Africa (SSA), home to around a fifth of the world’s population, bears a high burden of stroke with an age-standardized incidence rate of 160 per 100,000" Actually, this is not a high incidence. The incidence of stroke in Germany is around 250/100,000 per year "As the population of SSA is the 73 fastest growing and fastest ageing of all world regions" Please clarify this sentence. In table S1: Please explain what do you mean by the following terminologies: instable plaque, thrombus, reduced blood flow velocity Minor mistake: table 1 is described as figure 1 Reviewer #2: Very interesting well- written article that discussed the proportion of stroke types among Malagasy population I have some comments that might help improve this nice article. Line 164: (BMI) was more than 25 kg/m2, being an index it should not have units Table 1: Length of hospital stay (days) (164, 104, 60) is a bit confusing → (days) should be (no of patients ) Then (days) should be in the next rows, same applied for Length of hospitalization until death Table 2: side of lesion was bilateral in 12.5% of cases however 70% of cases has Fazekas I -III which means that 70 % of patients have bilateral lesions. So, what do you mean here by bilateral lesions? You did not mention the causes of death in your patients (chest infection , respiratory failure , pulmonary embolism, expanding hge/ inf etc). This is very important to know because your mortality rate is relatively high 22%. What about the other important stroke risk factors like ischemic heart disease, oral contraceptive pills, migraine, atrial fibrillation, anticoagulants ? You should mention in the limitation section that being a tertiary-level hospital this may cause selection bias as you will receive more of complicated and severe cases and this might explain the relatively higher morality rate among your cohort. Reviewer #3: This single center retrospective study using CT-confirmed strokes only, could miss a lot of ischemic strokes like minor strokes , posterior circulation strokes and others for which a CT scan might not have been less useful Even demographic and clinical data were not equally thorough and self-reported medical history may lead to an underestimation of negative findings. clinical data on stroke severity was limited and no standardized data on stroke severity was available. All above mentioned might shed great doubt on the message of the study ****** 6. 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: Ahmed Elhfnawy Reviewer #2: No Reviewer #3: Yes: Ossama yassin mansour ******** [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. https://doi.org/10.1371/journal.pone.0276199.r001
Revision 1
14 Aug 2022 Author Response Dear Dr Chenette, We would like to thank you and the reviewers for the constructive and insightful comments on our previous submission. By incorporating the editor’s and reviewers’ suggestions, we believe that we were able to significantly improve the quality of this manuscript. Please find on the following pages a point-by-point response to each of the comments. Reviewer #1: 1. I do not think that this study represents the true stroke figures. The authors included patients with CT-confirmed stroke. A significant proportion of stroke patients would have a small infarction in MRI, which would not appear in CT. I think the authors should have included stroke patients meeting the old WHO definition of stroke, irrespective of the neuroimaging: acute-onset focal neurological deficits lasting more than 24hours. This would increase the proportion of ischemic stroke patients. Please consider adding this data to your study. Response: We thank the reviewer for pointing this out and fully agree with this comment. As non-contrast head CT is known to have low sensitivity for detecting ischemic strokes overall and performs even worse in patients with posterior fossa stroke, it would have been preferable to include patients based on the old WHO definition of stroke. However, the overall accuracy and completeness of the available medical records was poor. Most records did not specifically mention the suspicion or diagnosis of a stroke and did not contain standardized information on stroke severity or the clinical course during admission. Thus, using the old WHO definition of stroke would have drastically reduced our sample size and the overall reliability of results. Therefore, we identified cases based on the hospital’s emergency room register, from which we extracted all cases that had a neurological deficit of sudden onset. Of those, we included all patients whose medical record contained CT images of the brain showing an ischemic or hemorrhagic stroke. A particular strength of our study was that CT findings were not obtained from reports, but all images were digitized and read by an experienced neuroradiologist who entered the scan results into a standardized data collection form prior to analysis. To address the reviewer’s concern the following sentence is included in the limitation section of the manuscript (page 20, line 327-329): “Third, by including CT-confirmed strokes only, minor strokes for which a CT scan might not have been performed or posterior circulation strokes, for which CT imaging is known to be less sensitive, might be underrepresented.” 2. Moreover, I think a significant proportion of stroke patients in SSA would not present to the hospital, which would explain the relatively higher prevalence of hemorrhagic stroke in this study. Response: We fully agree with the comment that in general, only a minority of patients after stroke can be expected to present to a hospital in SSA. This might in particular affect more severe stroke cases. However, financial constraints are one of the main reasons for patients to forgo or delay care in SSA [1, 2]. Thus, a conspicuous strength of our study was the inclusion of stroke patients irrespective of an individual’s financial situation which is unique in Madagascar and likely reduced this selection bias. 3. "Sub-Saharan Africa (SSA), home to around a fifth of the world’s population, bears a high burden of stroke with an age-standardized incidence rate of 160 per 100,000" Actually, this is not a high incidence. The incidence of stroke in Germany is around 250/100,000 per year. Response: We thank the reviewer for spotting this error and apologize for our oversight. The age-standardized incidence rate is up to 316 per 100,000 for Sub-Saharan Africa. We have amended the sentence as follows (page 4, line 67-69): "Sub-Saharan Africa (SSA), home to around a fifth of the world’s population, bears a high burden of stroke with an age-standardized incidence rate of up to 316 per 100,000 [3]." 4. "As the population of SSA is the fastest growing and fastest ageing of all world regions..." Please clarify this sentence. Response: We apologize for the lack of clarity. Sub-Saharan Africa (SSA) has a very high fertility rate of 4.7 births per woman compared to 2.4 births worldwide [4]). At the same time, life expectancy is increasing more rapidly in SSA than anywhere else [5]. To improve clarity, we have amended the sentence as follows (page 4, line 72-74): “As the population of SSA is the fastest growing and life expectancy is increasing most rapidly of all world regions...” 5. In table S1: Please explain what do you mean by the following terminologies: instable plaque, thrombus, reduced blood flow velocity. Response: We agree with the reviewer that these terms were insufficiently defined. We amended the legend of Supplementary Table 1 as follows: “Supplementary Table S1. Carotid duplex sonography findings by stroke type: IS = ischemic stroke; HS = hemorrhagic stroke a Number and % if not indicated otherwise b unstable atherosclerotic lesion at risk of rupture c blood clot in carotid artery at risk of embolization d post-stenotic reduced blood flow velocity in internal carotid artery” 6. Minor mistake: table 1 is described as figure 1. Response: We agree with the reviewer that the journal’s requirement to insert a figure legend right after the paragraph in which the figure is cited can be confusing especially when a table and a figure legend are inserted together. We have changed the order of figure and table to improve readability of the manuscript. Reviewer #2: Very interesting well- written article that discussed the proportion of stroke types among Malagasy population. I have some comments that might help improve this nice article. 1. Line 164: (BMI) was more than 25 kg/m2, being an index it should not have units. Response: We thank the reviewer for spotting this. We deleted the unit. 2. Table 1: Length of hospital stay (days) (164, 104, 60) is a bit confusing → (days) should be (no of patients). Then (days) should be in the next rows, same applied for Length of hospitalization until death. Response: We apologize for the inconsistency and have adjusted the rows in the Table 1 as suggested by the reviewer for improved clarity and readability. 3. Table 2: side of lesion was bilateral in 12.5% of cases however 70% of cases has Fazekas I -III which means that 70 % of patients have bilateral lesions. So, what do you mean here by bilateral lesions? Response: We thank the reviewer for the opportunity to clarify this inaccuracy. The lesions we described in the first section of Table 2 refer to the stroke lesions. We found bilateral stroke lesions in 12.5% of cases. In addition to rating the stroke on CT, we included information on white matter lesions using the Fazekas Scale to provide additional information on chronic small vessel disease and cardiovascular risk [7]. We have amended Table 2 accordingly to clarify that we describe only stroke lesions in the first section of the table. 4. You did not mention the causes of death in your patients (chest infection, respiratory failure, pulmonary embolism, expanding hge/ inf etc). This is very important to know because your mortality rate is relatively high 22%. Response: We fully agree with the reviewer and are grateful for the opportunity to provide more details about the causes of death in the study population. Unfortunately, data quality on the secondary causes was poor and did not allow to distinguish between different causes of death. We included the following paragraph in our results section (page 15, line 249-252): “Most in-hospital deaths were directly attributed to the brain lesion (63.3%; 31/49, 95% CI: 49-77%). Secondary causes of death included chest infection, respiratory failure, and cardiac infarction.” 5. What about the other important stroke risk factors like ischemic heart disease, oral contraceptive pills, migraine, atrial fibrillation, anticoagulants? Response: We thank the reviewer for this comment. Unfortunately, details about these risk factors were documented very inconsistently in the available medical records. For most cases it remained unclear whether the information was missing, a risk factor had been ruled out or if screening had not been performed at all. Therefore, we decided to refrain from reporting on risk factors for which data was inaccurate or incomplete. 6. You should mention in the limitation section that being a tertiary-level hospital this may cause selection bias as you will receive more of complicated and severe cases and this might explain the relatively higher mortality rate among your cohort. Response: We fully agree with the reviewer that the selection of our study hospital might have contributed to a higher number of severe cases of stroke. We have included the following sentence in the limitations section of the manuscript (page 20 line 325-327): “Second, the study hospital being a tertiary-level referral hospital might have introduced a selection bias towards more severe cases of stroke, which might explain the relatively high mortality rate. Third...” Reviewer #3: This single center retrospective study using CT-confirmed strokes only, could miss a lot of ischemic strokes like minor strokes, posterior circulation strokes and others for which a CT scan might not have been less useful. Even demographic and clinical data were not equally thorough and self-reported medical history may lead to an underestimation of negative findings. Clinical data on stroke severity was limited and no standardized data on stroke severity was available. All above mentioned might shed great doubt on the message of the study. Response: We thank the reviewer for this comment. As also outlined in our responses to Reviewer 1, point 1 above we fully agree that it would have been preferable to include patients based on the clinical definition of stroke as well as to include more demographic and clinical data on stroke severity. However, overall accuracy and completeness of the available medical records for this retrospective analysis was poor. The points have been addressed in the limitations section of the manuscript with our initial submission (page 20, line 310-325): Our study has limitations. First, the results of our single-center study in an urban setting might not reflect the true community burden of stroke. However, access to healthcare including CT scans was free of charge at the study hospital for patients reducing selection bias otherwise introduced by a households' ability to pay. In addition, prompt imaging and comprehensive investigation would not have been feasible in a community-setting. Second, by including CT-confirmed strokes only, minor strokes for which a CT scan might not have been performed or posterior circulation strokes, for which CT imaging is known to be less sensitive, might be underrepresented. Third, while medical records including demographic and clinical data were available for all patients, they were not equally thorough and self-reported medical history may lead to an underestimation of negative findings. On the other hand, patients’ medical history was consistently assessed for relevant risk factors, like hypertension, in 96.9% of records. Fourth, clinical data on stroke severity was limited and no standardized data on stroke severity was available. Nevertheless, we used imaging characteristics to determine stroke severity. Last, our study was not designed to assess stroke prevalence or incidence, as the details of the source population from which the study hospital draws its patients from were unknown. Conducting research in a resource-restricted public health setting harbors additional challenges and limitations due to an overall lack of resources and poor data quality. In this manuscript, we draw from multiple data sources to best describe the proportion of stroke types in a hospital-based case-series in Madagascar’s capital Antananarivo, the only hospital in the country where patients can obtain a CT scan regardless of an individual’s financial situation. Despite a high burden of disease, scientific literature on stroke in Madagascar is scarce; there is a mere one-digit number of stroke studies from Madagascar. This lack of research draws an inconclusive picture, hampers efficient public health resource allocation in Madagascar, and adds to overall health inequity. There is an urgent need for more and better quality stroke data in SSA. References: 1. McLane HC, Berkowitz AL, Patenaude BN, McKenzie ED, Wolper E, Wahlster S, et al. Availability, accessibility, and affordability of neurodiagnostic tests in 37 countries. Neurology. 2015;85(18):1614-22. 2. Swindle RN, David. Barriers to Accessing Medical Care in Sub-Saharan Africa in Early Stages of COVID-19 Pandemic. Poverty and Equity Notes. Washington, DC. ©: World Bank; 2021. 3. Akinyemi RO, Ovbiagele B, Adeniji OA, Sarfo FS, Abd-Allah F, Adoukonou T, et al. Stroke in Africa: profile, progress, prospects and priorities. Nature Reviews Neurology. 2021;17(10):634-56. 4. World Bank. Fertility rate, total (births per woman): The World Bank Group; 2022 [Available from: https://data.worldbank.org/indicator/SP.DYN.TFRT.IN. 5. Wan He IA, Dzifa Adjaye-Gbewonyo. Africa Aging: 2020. U.S. Government Printing Office, Washington D.C. : U.S. Census Bureau; 2020. 6. Reutern G-Mv, Goertler M-W, Bornstein NM, Sette MD, Evans DH, Goertler M-W, et al. Grading Carotid Stenosis Using Ultrasonic Methods. Stroke. 2012;43(3):916-21. 7. Sharma R SS, Cascella M. White Matter Lesions. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562167/. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0276199.r002
19 Sep 2022 Decision Letter - Ismail Ibrahim Ismail, Editor PONE-D-22-13670R1Proportion of stroke types in Madagascar: a tertiary-level hospital-based case seriesPLOS ONE Dear Dr. Emmrich, 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. Please submit your revised manuscript by Nov 03 2022 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. 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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, Ismail Ibrahim Ismail, MD 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. [Note: HTML markup is below. Please do not edit.] 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 ******** 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 ****** 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: Please remove the terminologies: "unstable plaque" and "thrombus" from table S1. Actually, unstable plaque means plaque neovascularity or floating thrombus. I don't know if this is what the authors mean. I cannot understand what the authors mean by thrombus? Reviewer #2: (No Response) ****** 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: Ahmed Elhfnawy Reviewer #2: No ******** [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. https://doi.org/10.1371/journal.pone.0276199.r003
Revision 2
26 Sep 2022 Author Response Reviewer #1: Please remove the terminologies: "unstable plaque" and "thrombus" from table S1. Actually, unstable plaque means plaque neovascularity or floating thrombus. I don't know if this is what the authors mean. I cannot understand what the authors mean by thrombus? Response: We thank the reviewer for pointing this out and apologize for the imprecise terminology in the previous version. We acknowledge that by non-contrast enhanced duplex ultrasound the diagnostic accuracy to assess the stability of a plaque and the sensitivity to detect intraluminal thrombi is limited. We report the findings as recorded by the Malagasy physician performing the ultrasound examination. To better describe the findings, we added details of the classification used to assess stability and clarified the term “thrombus”. The legend for “unstable plaque” now reads as: “unstable atherosclerotic lesion at risk of rupture described as “echolucent” or “predominantly echolucent” corresponding to types 1 and 2 in the Gray-Weale classification [1].” We omitted the term “thrombus” and specified to “intraluminal thrombus” which is also reflected in the legend now to read as: “intraluminal carotid artery thrombus at risk of embolization” Attachments Attachment Submitted filename: Response to Reviewers_rev2.pdf https://doi.org/10.1371/journal.pone.0276199.r004
2 Oct 2022 Decision Letter - Ismail Ibrahim Ismail, Editor Proportion of stroke types in Madagascar: a tertiary-level hospital-based case series PONE-D-22-13670R2 Dear Dr. Julius Emmrich 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Ismail Ibrahim Ismail, MD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0276199.r005
Formally Accepted
5 Oct 2022 Acceptance Letter - Ismail Ibrahim Ismail, Editor PONE-D-22-13670R2 Proportion of stroke types in Madagascar: a tertiary-level hospital-based case series Dear Dr. Emmrich: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Ismail Ibrahim Ismail Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0276199.r006

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