PONE-D-20-02427

Mortality and its predictors among patients admitted with acute exacerbation of chronic obstructive respiratory diseases in Jimma Medical Center: Prospective cohort study

PLOS ONE

Dear Teshale Mega Ayele,

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.

We would appreciate receiving your revised manuscript by Jun 26 2020 11:59PM. When you are 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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We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Adrish

Academic Editor

PLOS ONE

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2. Thank you for including your ethics statement:  The full protocol of this study was submitted for Institutional Review Board (IRB: IHRPGD/549/109) of JUMC, for ethical approval. After informing the overall concern of the study and confidentiality, written informed consent was taken written letter sheets; for those patients with problem of speaking,

consent was requested from relatives.  

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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: Partly

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

Reviewer #1: 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

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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: No

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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: The manuscript, "Mortality and its predictors among patients admitted with acute exacerbations of chronic obstructive respiratory diseases in Jimma Medical Center: Prospective cohort study", by T. Mega and colleagues reports the outcomes of a cohort of patients admitted with COPD exacerbations to a referral hospital in a low-resource country. The study is descriptive, but still adds to our understanding of the outcomes for COPD patients in different countries. However, the study has several important limitations, which are outlined below:

1. There are several grammatical and spelling errors throughout the manuscript, which makes the manuscript difficult to read. For example, the third sentence of the fourth paragraph of the Background reads, "An indoor (like smoking), outdoor air pollution and occupational asthma gens were risks quantified for asthma in GBD". This sentence appears to be missing a word or phrase. Additionally, "gens" is a mistake, and the authors' intent is not clear regarding what word is meant to be in this sentence. The manuscript should be carefully reviewed and these errors corrected.

2. The study population is very small given that the hospital serves a population of 15 million. The authors should provide reasons for this.

3. The authors should provide specific criteria as to how the underlying diagnosis of asthma or COPD was made in the cohort patients.

4. The authors should provide some context for the demographic information of their cohort. Specifically, they should indicate whether there are specific differences between the patients and the rest of the communities served by Jimma Hospital, or if the patient cohort is generally representative of the surrounding areas.

5. There should be more details about the in-patient therapy received by the study cohort. Did any of the patients receive mechanical ventilation? What was the dose range and duration of steroid therapy used for treating the COPD/asthma exacerbations? This information will allow the interested reader to understand the differences in therapy received by the patients in the Jimma cohort and other COPD populations.6

6. The authors should summarize the post-hospital follow up provided to the patients. Was there a systematic post-discharge educational program given to the patients? Is there a community-based nursing follow up available?

7. The finding that patients with comorbid disease were less likely to die during follow up compared to patients without comorbidities is unexpected. The authors should enlarge their Discussion of this finding to include their assessment as to the reasons for this.

Reviewer 2

This is an interesting study and the objective of the study are well stated. In the introduction, the objectives are stated clearly: explore in-hospital  of asthma and COPD exacerbations in low-income nations.

Comments:

1) Title- while this study is from Jimma Ethiopia, the authors may want to re-consider their title and add Ethiopia after Jimma.

2) Sample size- the authors chose a 6 month study period with a relatively small 'N" of 130, did the authors consider extending the study period to 12 months to capture more patients.

3) Grammatical errors: There are numerous speling, syntax and grammatical errors throughout the manuscript which I have noted below.

3a) Abstract in methods: "Kaplan-Mayer  (Log-rank test) and Cox regression" The crrect spelling is Kaplan Meier.

3b) Abstract: "The total proportion of in-hospital mortality was 14(10.78%), making the incidence  rate of mortality, 2.56 per 1000 person-years; 95% CI [1.518-4.328]." The authros should re-word this sentence as it is unclear as written.

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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.

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Reviewer #1: 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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-02427R1

Mortality and its predictors among patients treated for acute exacerbations of chronic obstructive respiratory diseases in Jimma Medical Center; Jimma, Ethiopia: Prospective observational study

PLOS ONE

Dear Dr. Ayele,

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: I have received the comments of the reviewers on your manuscript. The specific comments of the reviewers are included below. Please provide point by point response in your revised manuscript.

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

Please submit your revised manuscript by due date. 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Adrish

Academic Editor

PLOS ONE

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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)

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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: Partly

**********

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: No

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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: No

**********

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: The revised manuscript by T. Mega and colleagues has been much improved by the authors’ revisions. However, this study continues to have significant limitations, which are summarized below:

1. While improved, the writing continues to have many spelling, grammar, and word choice errors. Examples of these include:

a. Line 108 “cathment” instead of “catchment”

b. Line 120 “miss diagnosed” instead of “misdiagnosed”

c. Line 169 “throghly” instead of “thoroughly”

d. Line 169 “discudssed” instead of “discussed”

e. Line 234 “Moreover” is awkward.

f. Line 247 “peviuos” instead of “previous”

g. Line 258 “chronic comorbidities and it contributed” - the subject of “contributed” should be plural

h. Line 337 “predictor” instead of “predictors”

i. Line 393 “prevents” is not the correct word to describe an inverse association between comorbid disease and mortality.

The authors need to have the manuscript reviewed again in detail to correct these English errors

2. The description of the study population would be improved by providing additional context for the interested reader. For example, how does the high prevalence of smoking (21.5%) in the study population compare to the overall prevalence in Ethiopia? Approximately half of the subjects were from rural areas – does this reflect the overall population in the hospital catchment area? Additionally, since a substantial percentage (56%) of the study subjects did not have formal education, what percentage of the general population in the hospital catchment area and/or Ethiopia similarly does not have formal education?

3. The authors should provide additional information about the use of antibiotics for the patients, particularly since their use correlated with mortality. Since the subjects were all admitted with exacerbations of lung disease, the number of subjects who did not receive antibiotics is high. Are there hospital guidelines regarding the use of antibiotics? If not, is there a consensus among the practitioners in the hospital regarding the use of antibiotics for patients admitted with exacerbations of lung disease? Is the use of antibiotics likely to be a marker of disease severity? Why did the authors not include statistics regarding antibiotic use?

4. The Discussion still includes a statement (line 393) that the presence of comorbid disease was protective. However, the findings reported in the Results indicate that pulmonary hypertension, heart failure, and renal dysfunction were all associated with increased mortality. This discordance should be resolved.

5. The authors need to expand their discussion of the study limitations. The small sample size resulted in the study lacking statistical power. The study therefore likely missed predictors of mortality. An example of this would be the lack of association between prior hospitalization and mortality. The authors need to more fully outline this limitation of their study. Additionally, the exclusion of patients requiring mechanical ventilation needs to be described as a limitation. Although the authors provide the rationale for this exclusion, patients who require mechanical ventilation for an exacerbation of lung disease have a high in-hospital mortality. Thus, excluding this population limited the study’s ability to detect risk factors for in-hospital mortality.

6. Table 5 has an asterisk after the number of night attacks. It isn't clear if this refers to something that should have additional clarification in the Table legend or if this is a typographical error. The authors should either clarify the use of the asterisk or remove it.

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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

[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.

Mortality and its predictors among patients treated for acute exacerbations of chronic obstructive respiratory diseases in Jimma Medical Center; Jimma, Ethiopia: Prospective observational study

PONE-D-20-02427R2

Dear Dr. Ayele,

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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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,

Muhammad Adrish

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: (No Response)

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

Reviewer #1: (No Response)

**********

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: (No Response)

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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: (No Response)

**********

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: (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