Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease, and chronic kidney disease: A systematic review and meta-analysis

Ryan J. Bamforth; Ruchi Chhibba; Thomas W. Ferguson; Jenna Sabourin; Domenic Pieroni; Nicole Askin; Navdeep Tangri; Paul Komenda; Claudio Rigatto

doi:10.1371/journal.pone.0249542

Peer Review History

Original SubmissionAugust 19, 2020
14 Sep 2020 Decision Letter - Hans-Peter Brunner-La Rocca, Editor PONE-D-20-21147 Strategies to prevent hospital readmission and death in patients with advanced chronic diseases: a systematic review and meta-analysis PLOS ONE Dear Dr. Rigatto, 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 note that both reviewers expressed important issues to improve the manuscript. I agree with them and would like to to address them and include the suggestions in the revised manuscript. Please submit your revised manuscript by Oct 29 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Hans-Peter Brunner-La Rocca, M.D. 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 https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. In your Methods section, please ensure you have stated the date of last search for studies in this review, ensuring it is up to date enough to allow the inclusion of studies published in the past 12 months. 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: "We gratefully acknowledge the support of the University of Manitoba Max Rady College of Medicine and the Chronic Disease Innovation Centre, Seven Oaks General Hospital." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "The author(s) received no specific funding for this work." Please include your amended statements within 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 Reviewer #2: 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 Reviewer #2: 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: Strategies to prevent hospital readmission and death in patients with advanced chronic diseases: a systematic review and meta-analysis Reviewer Recommendation and Comments for Manuscript Number PONE-D-20-21147 from Per Arne Holman. Summary of the research and your overall impression I congratulate the authors with a comprehensive literature review on an area of importance. This study aim to identify effective strategies to prevent hospital readmission and deaths in patients with chronic diseases. The focus of review is on three conditions and five strategies. This focus could be mentioned more explicit in the title and motivated more explicit in the introduction. This would help the reader to understand what to expect from the study. The strength of the study is the search method applied on a large number of articles published over the last 20 years. One limitation, not discussed in the paper, is that each strategy may have changed methodologically over so many years. Discussion of specific areas for improvement I have one major and one minor issue to address, which in my opinion would improve the manuscript without influencing the results. Major issue: The article should explain the reasoning more explicit for the scope chosen; three of many possible chronical conditions and the five strategies. In my opinion, it is unclear whether the results depend on the search method focusing particularly on the named five strategies in the chronic condition groups, or if the review identified only the five named strategies after a broad search, or if the five were the most promising of many. I would recommend to outline whether the literature search starts with, not land on, three patient groups (CHF, COPD, CKD) and five strategies (education, phone, visits, tele monitor and multidisciplinary team) in title or/and very early in the introduction. In the introduction (87) there is an anchor to article reference 8. If the authors give this article some more mentioning, it could help the reader to understand why that article frame the knowledge gap the intend to fill. From line 99 it would help to understand why you included the particular interventions in the search, and why possible others were left out, cf. line 142 where it is not clear either. (89) Is virtual wards a focus area in this article already before the systematic review of literature started? If so, should it be included in the title? A closer description of the strategies in the introduction or title would help the reader to understand the scope better; a comparison of “virtual wards” and “less complex and less costly interventions” . (Ref. 142-145) Virtual wards in not mentioned in the results nor in the discussion. Is virtual wards the same as telemonitoring strategy in the result section? Minor issue: The 20 years long period of inclusion face the challenge that each strategy identified may have changed over time. This is in particularly relevant for the introduction of modern technology in telemedicine in recent years. The results reported on literature from studies of CHF is based on 25 articles from 1999 to 2018. 15 studies are more than 10 years old. In the discussion I would have expected this article to comment on the fact that telemedicine as an intervention has undergone rapid changes, as indicated in the introduction when speaking of virtual wards; sensor technology (e.g. heart rate, blood pressure, dO2 and weight), PROMIS, video consultations and cellphones. One could expect that such interventions had been more promising and proven more effect on the outcomes in recent years. Apparently, there are few RCT studies on new telemedicine technology available yet. In my opinion this is something to be discussed. At least as an area for future studies. The authors could consider running the test again based on the 10 articles from the last decade, to see if telemedicine in fact produce higher interaction with the outcomes for CHF. I would expect to see changes in the way patient education is delivered to change in a more digital direction. Miscellaneous remarks (Abstract, 30, 74) The use of «Rehospitalization». The article use «readmission» mostly, but in the background section rehospitalization is introduced. I suggest a consistent use of readmission will clarify if there is a difference between the two. A definition of a readmission in the introduction would help the reader and might be useful to understand if different definitions may have affected the search of literature performed. (81) Discuss if 60% of hospital readmissions are preventable. I’m not an expert, by fare, in systematic literature of meta-analysis. However, I’ve gone through the supplements. The methods are, in my opinion, well described. I recommend the editor to invite peer reviewers with more expertise in this area. Reviewer #2: This is a well written article on an important topic and clearly a major undertaking. I am concerned that there is no discussion of other systematic reviews on this topic and how this study compares with these. A simple literature research brought up article such as: Leppin AL, Gionfriddo MR, Kessler M, Brito JP, Mair FS, Gallacher K, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-107. Gwadry-Sridhar FH, Flintoft V, Lee DS, Lee H, Guyatt GH. A systematic review and meta-analysis of studies comparing readmission rates and mortality rates in patients with heart failure. Arch Intern Med. 2004;164(21):2315-20. Rice H, Say R, Betihavas V. The effect of nurse-led education on hospitalisation, readmission, quality of life and cost in adults with heart failure. A systematic review. Patient Educ Couns. 2018;101(3):363-74. This study would benefit from a discussion of how this paper adds to previous systematic reviews such as those listed above. Please briefly discuss why CHF, COPD and CKD were chosen - I understand that these are the commonest conditions with heavy burden but it would be good to have some background to that for the reader. I could not see a time line for the search in the paper - on reviewing the search criteria - it appeared to be 2015-current yet there are studies from 1999 included - please clarify and state the timeline in the paper. Table 1 first paper intervention period -0.25 - this must mean one week but is a little confusing perhaps put 0.25(1w) for clarification. Line 268 - there are two "ins" ****** 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:** Per Arne Holman 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.0249542.r001
Revision 1
2 Feb 2021 Author Response Dear Dr. Heber Thank you for considering our manuscript for publication in PLOS One. Please find below our response to editors’ and reviewers’ comments 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 https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Response: Thanks you for the recommendation. Style requirements have been altered to meet journal requirements. 2. In your Methods section, please ensure you have stated the date of last search for studies in this review, ensuring it is up to date enough to allow the inclusion of studies published in the past 12 months. Response: Thank you, this has been included on page 5, line 110 and reads “We searched MEDLINE, PubMed, Cochrane, EMBASE and CINAHL identifying relevant studies published up to November, 2020”. 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: "We gratefully acknowledge the support of the University of Manitoba Max Rady College of Medicine and the Chronic Disease Innovation Centre, Seven Oaks General Hospital." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "The author(s) received no specific funding for this work." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: Thank you, we have included a revision in the cover letter and removed the statement from the manuscript. Reviewers' comments: Reviewer #1: Strategies to prevent hospital readmission and death in patients with advanced chronic diseases: a systematic review and meta-analysis Reviewer Recommendation and Comments for Manuscript Number PONE-D-20-21147 from Per Arne Holman. Summary of the research and your overall impression I congratulate the authors with a comprehensive literature review on an area of importance. This study aim to identify effective strategies to prevent hospital readmission and deaths in patients with chronic diseases. The focus of review is on three conditions and five strategies. This focus could be mentioned more explicit in the title and motivated more explicit in the introduction. This would help the reader to understand what to expect from the study. The strength of the study is the search method applied on a large number of articles published over the last 20 years. One limitation, not discussed in the paper, is that each strategy may have changed methodologically over so many years. Response: Thank you for the recommendation, we have altered the title to the following: “Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease: a systematic review and meta-analysis”. Discussion of specific areas for improvement I have one major and one minor issue to address, which in my opinion would improve the manuscript without influencing the results. Major issue: The article should explain the reasoning more explicit for the scope chosen; three of many possible chronical conditions and the five strategies. In my opinion, it is unclear whether the results depend on the search method focusing particularly on the named five strategies in the chronic condition groups, or if the review identified only the five named strategies after a broad search, or if the five were the most promising of many. I would recommend to outline whether the literature search starts with, not land on, three patient groups (CHF, COPD, CKD) and five strategies (education, phone, visits, tele monitor and multidisciplinary team) in title or/and very early in the introduction. In the introduction (87) there is an anchor to article reference 8. If the authors give this article some more mentioning, it could help the reader to understand why that article frame the knowledge gap the intend to fill. From line 99 it would help to understand why you included the particular interventions in the search, and why possible others were left out, cf. line 142 where it is not clear either. (89) Is virtual wards a focus area in this article already before the systematic review of literature started? If so, should it be included in the title? A closer description of the strategies in the introduction or title would help the reader to understand the scope better; a comparison of “virtual wards” and “less complex and less costly interventions” . (Ref. 142-145) Virtual wards in not mentioned in the results nor in the discussion. Is virtual wards the same as telemonitoring strategy in the result section? Response: Thank you for the recommendation. Our literature search began with the three patients groups and after reviewing the literature we identified the 5 types of post-discharge interventions. Additionally, we have altered the title to the following: “Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease: a systematic review and meta-analysis”. Minor issue: The 20 years long period of inclusion face the challenge that each strategy identified may have changed over time. This is in particularly relevant for the introduction of modern technology in telemedicine in recent years. The results reported on literature from studies of CHF is based on 25 articles from 1999 to 2018. 15 studies are more than 10 years old. In the discussion I would have expected this article to comment on the fact that telemedicine as an intervention has undergone rapid changes, as indicated in the introduction when speaking of virtual wards; sensor technology (e.g. heart rate, blood pressure, dO2 and weight), PROMIS, video consultations and cellphones. One could expect that such interventions had been more promising and proven more effect on the outcomes in recent years. Response: Thank you for the recommendation. We have included additional analyses which excludes studies in heart failure published prior to 2009. The results remain consistent with calculated risk ratios being of similar direction and magnitude. Miscellaneous remarks (Abstract, 30, 74) The use of «Rehospitalization». The article use «readmission» mostly, but in the background section rehospitalization is introduced. I suggest a consistent use of readmission will clarify if there is a difference between the two. A definition of a readmission in the introduction would help the reader and might be useful to understand if different definitions may have affected the search of literature performed. Response: Thanks you for the recommendation. Line 19 has been changed to read readmission rather than rehospitalization. (81) Discuss if 60% of hospital readmissions are preventable. Response: Thank you for the recommendation. This has been addressed no page 4, line 74 and reads the following It has been estimated that nearly 60% of hospital readmissions are preventable (4). Risk factors associated with avoidable readmissions include those related to patient, social, clinical and system factors such as patient behaviors, community services, adequacy and appropriateness of assessment and treatment as well as accessibility and coordination within the healthcare delivery system (4). I’m not an expert, by fare, in systematic literature of meta-analysis. However, I’ve gone through the supplements. The methods are, in my opinion, well described. I recommend the editor to invite peer reviewers with more expertise in this area. Reviewer #2: This is a well written article on an important topic and clearly a major undertaking. I am concerned that there is no discussion of other systematic reviews on this topic and how this study compares with these. A simple literature research brought up article such as: Leppin AL, Gionfriddo MR, Kessler M, Brito JP, Mair FS, Gallacher K, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-107. Gwadry-Sridhar FH, Flintoft V, Lee DS, Lee H, Guyatt GH. A systematic review and meta-analysis of studies comparing readmission rates and mortality rates in patients with heart failure. Arch Intern Med. 2004;164(21):2315-20. Rice H, Say R, Betihavas V. The effect of nurse-led education on hospitalisation, readmission, quality of life and cost in adults with heart failure. A systematic review. Patient Educ Couns. 2018;101(3):363-74. This study would benefit from a discussion of how this paper adds to previous systematic reviews such as those listed above. Response: Thank you for the recommendation. This has been addressed on page 46 line 336 and reads Previous systematic reviews have found that interventions including patient education, home visits, self-management support, and telemonitoring have been effective in reducing hospital readmissions (48-52). As such, these findings support those reported in our previous work (8) and are broadly consistent with recent systematic reviews in heart failure (49-52). Thus, there appears to be strong evidence for efficacy of post-discharge interventions in heart failure patients. This research adds to previous systematic reviews by including more recently published studies as well as by analyzing the presence of an era effect in heart failure studies”. Additionally, we have altered line 350 on page 46 to read ” Other systematic reviews have found that interventions with increased complexity were more effective in reducing hospital readmissions compared to less complex interventions:. Please briefly discuss why CHF, COPD and CKD were chosen - I understand that these are the commonest conditions with heavy burden but it would be good to have some background to that for the reader. Response: Thank you for the comment. We have address this on Page 6, line 120 and it reads “We focused specifically on CKD, HF, and COPD as these chronic diseases place heavy burdens on modern health systems with respect to prevalence, resource utilization and costs”. I could not see a time line for the search in the paper - on reviewing the search criteria - it appeared to be 2015-current yet there are studies from 1999 included - please clarify and state the timeline in the paper. Response: Thank you for bringing this to our attention. We have amended the manuscript on page 5, line 110 which states the timeline. The initial search went back as far as each database goes with it ending in November, 2020. Table 1 first paper intervention period -0.25 - this must mean one week but is a little confusing perhaps put 0.25(1w) for clarification. Response: Thank you for the recommendation, The intervention period in table 1 has been amended to read 0.25 (1 week). Line 268 - there are two "ins" Response: Thank you for the comment. The duplicate “in” has been removed from the text at line 268. Sincerely, Dr. Claudio Rigatto Head, Section of Nephrology, University of Manitoba Associate Medical Director, Manitoba Renal Program Seven Oaks General Hospital crigatto@sbgh.mb.ca 204-632-3383 On behalf of: Ryan J. Bamforth, Ruchi, Chhibba, Thomas W. Ferguson, Jenna Sabourin, Domenic Pieroni, Nicole Askin, Navdeep Tangri and Paul Komenda. https://doi.org/10.1371/journal.pone.0249542.r002
25 Feb 2021 Decision Letter - Hans-Peter Brunner-La Rocca, Editor PONE-D-20-21147R1 Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease: a systematic review and meta-analysis PLOS ONE Dear Dr. Rigatto, 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. There are some remaining issues that need to be addressed before your paper can be accepted for publication. Please consider to have your manuscript copy-edited by a native speaking person as there is not such editing for PLOS ONE. Please submit your revised manuscript by Apr 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: 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, Hans-Peter Brunner-La Rocca, M.D. 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: (No Response) ******** 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: 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: (No Response) Reviewer #2: Thank your for addressing the issues raised in the first review. There are still a few minor typos and punctuation issues so please review for this. My only concern is that you have addressed why you chose the clinical areas for review CHF, COPD and CKD but this is in the methods - I think it need to be in the introduction immediately after you state the clinical areas reviewed, especially as you have added references which are not really appropriate in the methods section, but would work well in the introduction. That is - this sentence needs to be in the intro. “We focused specifically on CKD, HF, and COPD as these chronic diseases place heavy burdens on modern health systems with respect to prevalence, resource utilization and costs”. Other wise I have no other comments and this is Avery useful addition to the literature. ****** 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: Per Arne Holman Reviewer #2: Yes:** Professor Carol J. Peden [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.0249542.r003
Revision 2
16 Mar 2021 Author Response March 16, 2021 Dr. Joerg Heber Editor-in-Chief, PLOS One Dear Dr. Heber Thank you for considering our manuscript for publication in PLOS One. Please find below our response to editors’ and reviewers’ comments 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. Response: Thank you for outlining this. The reference list has been reviewed for retracted papers as well as formatted to be complete and correct. Reviewers' comments: Reviewer #2: Thank your for addressing the issues raised in the first review. There are still a few minor typos and punctuation issues so please review for this. My only concern is that you have addressed why you chose the clinical areas for review CHF, COPD and CKD but this is in the methods - I think it need to be in the introduction immediately after you state the clinical areas reviewed, especially as you have added references which are not really appropriate in the methods section, but would work well in the introduction. That is - this sentence needs to be in the intro. “We focused specifically on CKD, HF, and COPD as these chronic diseases place heavy burdens on modern health systems with respect to prevalence, resource utilization and costs”. Response: Thank you for the recommendation. We removed the sentence from the methods section and added the following sentence to the introduction on page 5 line 100: “We chose these conditions because all of them are common and associated with frequent and costly exacerbations/acute decompensations necessitating admission for stabilization and associated with high risk of recurrence.” Additionally, the manuscript has been edited to address all spelling, punctuation and grammar errors. We thank you for bringing this up. Sincerely, Dr. Claudio Rigatto Head, Section of Nephrology, University of Manitoba Associate Medical Director, Manitoba Renal Program Seven Oaks General Hospital crigatto@sbgh.mb.ca 204-632-3383 On behalf of: Ryan J. Bamforth, Ruchi, Chhibba, Thomas W. Ferguson, Jenna Sabourin, Domenic Pieroni, Nicole Askin, Navdeep Tangri and Paul Komenda. https://doi.org/10.1371/journal.pone.0249542.r004
22 Mar 2021 Decision Letter - Hans-Peter Brunner-La Rocca, Editor Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease, and chronic kidney disease: a systematic review and meta-analysis PONE-D-20-21147R2 Dear Dr. Rigatto, 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, Hans-Peter Brunner-La Rocca, M.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0249542.r005
Formally Accepted
12 Apr 2021 Acceptance Letter - Hans-Peter Brunner-La Rocca, Editor PONE-D-20-21147R2 Strategies to prevent hospital readmission and death in patients with chronic heart failure, chronic obstructive pulmonary disease, and chronic kidney disease: a systematic review and meta-analysis Dear Dr. Rigatto: 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. Hans-Peter Brunner-La Rocca Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0249542.r006

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