https://orcid.org/0000-0002-7921-2721
Peer Review History
| Original SubmissionApril 11, 2021 |
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PONE-D-21-11999 Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020 PLOS ONE Dear Dr. Bogdanic, 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 make necessary changes as per reviewer comment. And submit accordingly. Please submit your revised manuscript by Jul 10 2021 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:
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. 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, Prasenjit Mitra, MD, MRSB, MIScT, FLS, FACSc, FAACC Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 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 2. 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. 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 4.Thank you for stating the following in the Financial Disclosure section: "The author(s) received no specific funding for this work." We note that one or more of the authors are employed by a commercial company: Zagreb City Pharmacy a) Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form. 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The specific roles of these authors are articulated in the ‘author contributions’ section.” If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement. b) Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc. Within your Competing Interests Statement, please confirm that this commercial affiliation 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) . 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Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests [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 ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ********** 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 ********** 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 ********** 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 want to compliment the authors. This is a well written manuscript, giving very interesting information, with lessons to be learned for the future. I have some remarks/suggestions for the authors to consider, that I hope could further strengthen their case. Abstract: - from 2017 to 2020 (1.76, 1.91, 1.91 and 2.01/1000 inhabitant-days, respectively) � suggestion for clarity: increased in 2017, 2018, 2019 and 2020 - Azithromycin distribution to pharmacies was the largest in March 2020 which indicates that fear of a great epidemic can influence consumption of antimicrobials with unproven benefits for the disease in question. Our data indicate that azithromycin overuse was also present during the second wave of the COVID-19 epidemic in Croatia. � I think the DOT over the years is the best measure of AZ overconsumption, as the monthly DOT are difficult to interpret. Distribution is, as the authors correctly state in the limitations, not the same as use; and we can assume that with the quick succession of scientific reports on this issue, it will have been very difficult to attune supply and demand. While I agree that the monthly evolution is described in the abstract, I would personally leave it out of the conclusion. � I think it is rather bold to assume that fear has been the main drive for azithromycin consumption. Also, until October, there were to my knowledge still only two randomized controlled trials (Cavalcanti et al, Furtado et al), in which azithromycin was mostly combined with hydroxychloroquine (overview doi: 10.1136/bmjresp-2020-000806). I agree that AZ should have ideally only been prescribed in a context of randomized controlled trials. However, with the conflicting data (and no direct safety issues reported with AZ monotherapy) I can understand why hospitals with more limited resources (in terms of dedicated study personnel) would have chosen to use AZ outside of studies until the results of RECOVERY were widely known. I think this sentence “ Preliminary information on COVID-19 treatments with a desire to offer and try what is available even in the absence of strong scientific evidence might have influenced practices of antimicrobial prescriptions.” Is much stronger, closer to the truth and suits the conclusion better. I would rather reform the current sentence in the conclusion as a question for the introduction, e.g. “could fear of a great epidemic influence consumption of antimicrobials with unproven benefits?”, or else raise this issue in the discussion. - About the 8.1% increase compared to the mean of 2017-2019 o Compared to 2018-2019 the increase is only 5%. I have no view on AZ prescription in Croatia, but I feel their case would be stronger if AZ prescription over the last 5 years was mentioned instead of only the last 3. Given that this makes the figure more complex, I would understand why the authors would stick to 3 years, but I would kindly ask if they could provide me those numbers then. o I presume that in Croatia too, a significant part of AZ prescription will be chronic AZ use (e.g. 3 weekly doses for COPD), which of course greatly influences the DOT/1000 inhabitant days. I wonder if the average reader will be aware of the fact that an 8,1% increase is therefore more important than it looks at first sight, because treatment duration for COVID is shorter. An absolute increase of 0.15DOT/1000inhabitant days is quite abstract, but in a population of approximately 4000000inhabitants, and given that a normal AZ treatment course for COVID would be 5 days, I’d say that about an extra 43000 patients (!!) were treated with AZ. I would even suspect that the true overconsumption due to COVID has been larger. One should subtract from the mean of 2017-2019 also the number of cases that have not been treated from atypical pneumonia in the Influenza season, which was considerably less than previous years due to isolation measures. The latter is marginally mentioned in the manuscript but could be emphasized more to underline the magnitude of the increase. - AZ monotherapy seems safe from the available data. However, combination with HQ or with other antibiotics on ICU raises concerns for cardiac adverse events and warrants close monitoring. This could be emphasized in the discussion and related to the significant increase in (often frail) patients that have been exposed to the drug. - At the other hand, for the authors, the most important concern on the long-term is probably microbial resistance against macrolides. For this I personally think that it is reassuring that the relative increase has ONLY been 8%. I think that the discussion would be stronger if the authors could elaborate on that. o E.g. do they think that this 8% increase in DOT, which will have mostly been spread over short treatment courses (causing less resistance than chronic treatment) of approximately 5 days, will have a significant impact on bacterial resistance? To the best of my knowledge, there is no data for my own country yet… is ther for Croatia? o Are we lucky that COVID mitigation strategies caused an unusually mild influenza season (influenza having a notoriously larger number of bacterial coinfections than COVID-19), which has somewhat compensated for the ungrounded increase of AZ in the treatment of COVID? I have no additional comments Kind regards ********** 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: Iwein Gyselinck [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. |
| Revision 1 |
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PONE-D-21-11999R1 Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020 PLOS ONE Dear Dr. Bogdanic, 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: Please check the reviewers comments... Please submit your revised manuscript by Sep 11 2021 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:
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. 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, Prasenjit Mitra, MD, MRSB, MIScT, FLS, FACSc, FAACC 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 ********** 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 ********** 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: Again I compliment the authors with the well written article, providing insight in azithromycin use, something many suspect but few have published upon. I have some minor suggestions left. No need for re-review after this. Best wishes IG Abstract: I would change the order of sentences to draw first attention to the real solid conclusion of the manuscript. Also maybe better “the period”. Also I’d dare to use may instead of might (stronger). => Our data showed increased azithromycin distribution in the period 2017 – 2020 which indicates azithromycin overuse. Preliminary information on COVID-19 treatments with a desire to offer and try what is available even in the absence of strong scientific evidence may have influenced practices of antimicrobial prescriptions. Discussion: * Galotti et al. analyzed Twitter messages posted during the early stages of the COVID-19 pandemic and found that potentially unreliable information preceded the rise of COVID-19 cases [8]. I’m not sure that I get this sentence. The way I interpret it, is that in the early pandemic, there was a lot of misinformation. The way it is formulated though, one gets the impression that the rise of COVID-19 cases has anything to do with the previous misinformation. To avoid any confusion, I’d maybe say: => Galotti et al. analyzed Twitter messages posted from January to March 2020, and found an increase in potentially unreliable information in those early stages of the COVID-19 pandemic [8]. * This indicates that fear of a great epidemic and uncertainty due to the absence of the treatment with proven efficacy can influence consumption of antimicrobials with assumed or unproven benefits. Still think “indicates” is somewhat strong based only on the associations given before. If I may add a couple of suggestions: => This supports the idea/This supports the thesis/It thus seems… that fear of a great epidemic and uncertainty due to the absence of the treatment with proven efficacy can influence consumption of antimicrobials with assumed or unproven benefits. * Isolation measures and social distancing during 2020 probably contributed to fewer acute respiratory infections including influenza and atypical pneumonia which is the common reason for azithromycin use during the influenza season. => Maybe “post-influenza pneumococcal infection” instead of influenza? ********** 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: Iwein Gyselinck [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. |
| Revision 2 |
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PONE-D-21-11999R2Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020PLOS ONE Dear Dr. Bogdanic, 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: Please look into the reviewer's comments ============================== Please submit your revised manuscript by Nov 07 2021 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:
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, Prasenjit Mitra, MD, CBiol, MRSB, MIScT, FLS, FACSc, FAACC 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 (if provided): [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 ********** 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) ********** 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 ********** 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: - ... fewer acute respiratory infections including post-influenza pneumococcal infection and atypical pneumonia which is THE common reason for azithromycin use during the influenza season ...: use A common reason instead of THE - ... So, the facts that there was no significant influenCa epidemic would indicate that the increase in azithromycin...: typo influenZa ********** 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: Iwein Gyselinck [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. |
| Revision 3 |
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PONE-D-21-11999R3 Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020 PLOS ONE Dear Dr. Bogdanic, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we have decided that your manuscript does not meet our criteria for publication and must therefore be rejected. I am sorry that we cannot be more positive on this occasion, but hope that you appreciate the reasons for this decision. Yours sincerely, Farzad Taghizadeh-Hesary Academic Editor PLOS ONE Editor Comments: Summary: To report the rate of azithromycin administration over the pandemic and to find a correlation with Covid-19 cases. Overall scoring (1-5) 1. Novelty: 3 2. Writing: 4 3. Methodology: 2 4. Data presentation: 3 5. Data interpretation: 3 Major concerns: - Statistical analysis: A investigator needs to examine three assumptions to run Spearman's Rank-Order Correlation test. 1. Type of variables: ordinal, interval, or ratio scale 2. Paired observation 3. Monotonic relationship In this study, the 2nd assumption is not considered. And, the 3rd one is not addressed. - This study has tried to rule out the effect of other factors influencing the rate of macrolide consumption by referring to studies of other countries (for example, coinfection to a study from North California, or Influenza to a general report from Europe). To make the results more reliable, the investigators need to evaluate and rule out the other reasons for azithromycin overuse during the pandemic IN CROATIA. Comments: - it is suggested to improve the clinical implications of the study with the following two suggestions: 1. to add the information of azithromycin adverse effects during the pandemic. 2. to compare the covid-19 mortality based on a rate of azithromycin administration. [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 ********** 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 ********** 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: (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: Iwein Gyselinck, MD Clinical Resident Respiratory Diseases, (subgroup), UZ Leuven PhD student BREATHE, department CHROMETA, KU Leuven Campus Gasthuisberg - O&N1bis Herestraat 49 bus 706 B-3000 Leuven, Belgium [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.] - - - - - For journal use only: PONEDEC3 |
| Revision 4 |
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PONE-D-21-11999R4Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020PLOS ONE Dear Dr. Bogdanic, 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 revise the statistical application and data presentation as recommended by the reviewer. Please see the comments directly on the manuscript. ============================== Please submit your revised manuscript by Feb 11 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. Please include the following items when submitting your revised manuscript:
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Kind regards, Iddya Karunasagar Academic Editor PLOS ONE Journal Requirements: Additional Editor Comments (if provided): Please see the comments of the expert on statistics. Please apply statistics as recommended by the reviewer and modify the presentation of data. [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 #2: All comments have been addressed Reviewer #3: 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 #2: Yes Reviewer #3: Partly ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: No Reviewer #3: I Don't Know ********** 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 #2: Yes Reviewer #3: (No Response) ********** 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 #2: Yes Reviewer #3: (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 #2: Comments • To study the correlation authors can modify the plot by taking independent variable (No of Covid -19 cases) on X- axis and dependent variable (Azithromycin usage) on Y- axis as per below (reference plot). Exclude the monthly distribution data for this analysis. Graph representing monthly distribution can still be retained and explained separately. Spearman correlation is employed when two variables are monotonically related. Which means all the data should be entirely in an increasing trend or in a decreasing trend and not a combination of both. The present data doesn’t strictly follow a monotonous relation neither a linear relation (Azithromycin usage in the month of march is an outlier) Authors can explore qualities of both correlation test (Pearson’s product moment and spearman’s rank correlation) and write the discussion accordingly For instance, spearman’s correlation explains the strength of monotonous relation, so the explanation for this could be how strict the data was in terms of monotonous relation (every increase in Covid-19 case resulting in increase of azithromycin usage) Pearson’s correlation explains strength of linear correlation, so the explanation for this could be if the rate of increase in the Azithromycin usage was constant for every increase in Covid-19 case • Comparison between monthly usage of Azithromycin for the year 2020 and the average use of azithromycin for the period 2017-2019 could be tested for significance. Authors can use ANOVA pair wise comparison and rate the difference as per p-value which can be denoted in graph using asterisks Reviewer #3: The article looks interesting, not very hard earned statistical paper but good evidence is present. the study is not a part of dual publication. the concern in the science is good enough ********** 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 #2: Yes: Caroline DSouza Reviewer #3: 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.
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| Revision 5 |
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Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020 PONE-D-21-11999R5 Dear Dr. Bogdanic, 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 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, Iddya Karunasagar Academic Editor PLOS ONE Additional Editor Comments (optional): Though technically the manuscript is now in an acceptable form, the authors may note the reviewers comments on the questions raised and answers provided by the authors. 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 #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 #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: • Authors have provided long explanation to justify ‘monotonous relation is not a prerequisite’ which was totally unnecessary It was clearly mentioned to authors that they can explore the qualities of both tests. Spearman correlation explains the strength of monotonous relation” (written in the comment) thus authors were asked to write the discussion accordingly. Also, in the previous comments it was clearly mentioned what monotonic relation means in the context of analysis done by the authors. • “you can run a Spearman's correlation on a non-monotonic relationship to determine if there is a monotonic component to the association “ Explanation provided by the authors is clearly aligned with review given earlier. So, the whole lot of explanation in this aspect doesn’t serve the purpose for which it was asked • We also provided additional statistical analysis but would like to stress again that this study was not planned as a hypothesis-driven study. We simply wanted to present descriptive data on azithromycin distribution between 2017 to 2020. We present our main data in absolute numbers of DOTs based on 1000 inhabitants-days of azithromycin Distribution For the fact that it is mentioned by the authors “There was a positive correlation between the number of COVID-19 cases and the total azithromycin consumption from July to December 2020 (Spearman’s test, ρ=0.94, p=0.005).” authors were asked to produce a statistical evidence and nowhere it was asked to make this as the main focus. All the conclusions drawn from the study also highlights azithromycin over-usage during COVID -19. Rp =Pearson’s product moment correlation coefficient, Rs = Spearman’s rank correlation coefficient can be added in the footnote. • Authors state “But does this formal statistical analysis of the mean monthly comparison for the whole year make sense if you look at the pattern of monthly distribution (see graphs)?” in contrary authors explain “Among non-hospital pharmacies, azithromycin distribution in March 2020 was 2.18 times higher” “1.93 and 1.84 times higher in November and December 2020” “In April-August 2020 the distributed DOT of azithromycin was not only lower than in other months of 2020, but also lower than the average in April-August 2017–2019 for both hospital and non-hospital pharmacies”” In fact, the distributed DOT of azithromycin in April-June 2020 was statistically significantly lower compared to the average of 2017–2019 (Table A in the S1 supporting information)” Authors are not asked to provide pooled data (whole year or quarterly) which becomes nonsignificant because of the large variation and outliers. Since there is no daily data on azithromycin usage (reported by the authors presently) test of significance for comparison between the months can avoided. • Also, the nonsignificant P-values derived from the above-mentioned analyses should not be interpreted as absence of overconsumption of azithromycin in 2020. Almost 38 000 extra 5-day courses of azithromycin were distributed in 2020 compared with previous years, with no obvious other reasons but COVID-19 which is quite relevant despite „nonsignficant“ P. Authors have done some analysis by grouping the data on their own and explained why it is not relevant which was not asked anywhere. • Of note, COVID-19, as discussed in our paper, should not be treated with azithromycin. Let’s not loose common sense when interpreting data. Correlational test with significant r value doesn’t show a causal relation and rather it only shows association. Authors can use appropriate language while answering the comments. Of note, Covid-19 even otherwise whether concluded in this paper or not, is to be treated with antivirals and not antibiotics. Authors are asked to read comments carefully before being opinionated. Sticking to the point with scientific facts and research proof would be appreciated. ********** 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 #2: No |
| Formally Accepted |
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PONE-D-21-11999R5 Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020 Dear Dr. Bogdanić: 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. Iddya Karunasagar Academic Editor PLOS ONE |
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