The influence of diagnostic subgroups, patient- and hospital characteristics for the validity of cardiovascular diagnoses–Data from a Norwegian hospital trust

Cathrine Sæthern Rye; Anne Pernille Ofstad; Bjørn Olav Åsvold; Pål Richard Romundstad; Julie Horn; Håvard Dalen

doi:10.1371/journal.pone.0302181

Peer Review History

Original SubmissionNovember 16, 2023
9 Jan 2024 Decision Letter - Vikramaditya Samala Venkata, Editor PONE-D-23-36180The influence of diagnostic subgroups, patient- and hospital characteristics for the validity of cardiovascular diagnoses – Data from a Norwegian hospital trusPLOS ONE Dear Dr. Rye, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Feb 23 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Vikramaditya Samala Venkata 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 the online submission form, you indicated that "Data cannot be shared publicly to protect participants privacy, due to containing personal identifiable and sensitive data. (European GDPR rules). Data are available from the Helse Nord Trøndelag Institutional Data Access, and may be shared upon reasonable request for researchers who meet the criteria for access to confidential data." All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 3. 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: Article is well written, just needs a few questions answered as noted by reviewers below. Please refer to the reviewer comments below [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: The manuscript "The influence of diagnostic subgroups patient- and hospital characteristics for the validity of cardiovascular diagnoses – Data from a Norwegian hospital trust" presents a comprehensive analysis of the validity of cardiovascular diagnoses, specifically acute myocardial infarction (AMI), heart failure (HF), and cerebrovascular diseases, in a hospital setting. The study involving 7164 patients aims to understand how different factors affect the accuracy of these diagnoses, which is crucial for epidemiological studies and patient care. Technical Soundness and Data Support: Statistical Analysis: The use of positive predictive values (PPV) and sensitivity as key metrics is appropriate for this study. The presentation of results, including the specific PPVs for different conditions and patient situations (inpatient vs. outpatient, primary vs. subsequent diagnoses), provides a detailed understanding of the factors influencing diagnostic accuracy. It seems that the statistical methods used, including Chi Square tests and logistic regression, are suitable for the data and research questions. Data Interpretation: The conclusion that diagnoses of AMI and stroke have high validity, especially when made during hospital stays, and that HF diagnoses are most valid when supported by echocardiography, is well-supported by data. These findings are significant and may have implications for the use of hospital discharge diagnoses in epidemiological studies. Data Availability and Ethical Compliance: Data Restrictions: It is noted that there are some restrictions on the availability of data. While it is understandable that patient privacy and compliance with GDPR rules might limit data sharing, this could potentially restrict the ability for independent verification of results. It would be beneficial if the data could be made available in a de-identified format to other researchers upon reasonable request. Ethical Compliance: The study's approval by the Regional Committee for Medical and Health Research Ethics of Mid-Norway and adherence to the Declaration of Helsinki are commendable. This ensures that the study meets high ethical standards. Manuscript Presentation: Clarity and Language: The manuscript is well-written and presents the research in a clear and understandable manner. The use of standard English and clear articulation of the research methods and findings makes the manuscript accessible to readers. Competing Interests and Funding: The declaration that there are no competing interests is noted. It's important for maintaining the objectivity of the study. However, information regarding specific funding sources or grants, if any, was not mentioned. Including this information would provide transparency about the potential influences on the research. Recommendations: Data Sharing: Consider providing a more detailed explanation of the data restrictions and potential ways researchers can access the data while still complying with GDPR and privacy concerns. Sub-Categories Analysis: Further elaboration on the validity of different sub-categories of diagnoses would be beneficial. This could provide deeper insights into which specific types of diagnoses are more or less reliable. Future Research Directions: Suggestions for future research, especially on how to improve the validity of diagnoses with lower PPV like TIA, would be beneficial. This could guide subsequent studies in this area. Reviewer #2: Excellent article that is very well written. Results are well presented and conclusions including limitations are well discussed. A couple of minor points - One of the limitations is that this study is applicable mainly to the HUNT system and demonstrates the fidelity of their diagnoses. Unsure of the generalizability across other study groups - As mentioned in the limitation section, ideally all cases should have been reviewed by at least two cardiologists if not more. This does limit the validity of conclusions slightly. Consider a repeat study in the future with better validation if possible ****** 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: HARPREET SINGH GREWAL Reviewer #2: Yes: Venkata Buddhavarapu ******** [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.0302181.r001
Revision 1
22 Feb 2024 Author Response PONE-D-23-36180: The influence of diagnostic subgroups, patient- and hospital characteristics for the validity of cardiovascular diagnoses – Data from a Norwegian hospital trust. We thank the Editor and the reviewers for their thoughtful comments and efforts to improve the manuscript. The constructive feedback from both reviewers is much appreciated. We have considered the reviewer comments carefully and made changes accordingly. Please see our replies below the comments. We hope that the revised manuscript will have sufficient priority for publication in PLOS ONE. Authors’ response to the point raised by the Academic Editor 1. Style and formatting requirements: To the best of our knowledge, the main body of the manuscript and the title page are edited and formatted according to PLOS ONE’s style template. 2. Data availability: Based on your kind feedback and PLOS journals requirements, we have now ensure that all underlying data used in the manuscript will be made freely available from the repository of Norwegian University of Science and Technology (DataverseNO) under the CC0 (Creative Commons Zero) license. 3. Reference list: The references has now been revised accordingly. Review Comments by Reviewer #1 The manuscript "The influence of diagnostic subgroups patient- and hospital characteristics for the validity of cardiovascular diagnoses – Data from a Norwegian hospital trust" presents a comprehensive analysis of the validity of cardiovascular diagnoses, specifically acute myocardial infarction (AMI), heart failure (HF), and cerebrovascular diseases, in a hospital setting. The study involving 7164 patients aims to understand how different factors affect the accuracy of these diagnoses, which is crucial for epidemiological studies and patient care. Technical Soundness and Data Support: Statistical Analysis: The use of positive predictive values (PPV) and sensitivity as key metrics is appropriate for this study. The presentation of results, including the specific PPVs for different conditions and patient situations (inpatient vs. outpatient, primary vs. subsequent diagnoses), provides a detailed understanding of the factors influencing diagnostic accuracy. It seems that the statistical methods used, including Chi Square tests and logistic regression, are suitable for the data and research questions. Data Interpretation: The conclusion that diagnoses of AMI and stroke have high validity, especially when made during hospital stays, and that HF diagnoses are most valid when supported by echocardiography, is well-supported by data. These findings are significant and may have implications for the use of hospital discharge diagnoses in epidemiological studies. Authors’ response: Thank you for the comprehensive evaluation. We have no further comments to the above listed comments by reviewer 1. Data Availability and Ethical Compliance: Data Restrictions: It is noted that there are some restrictions on the availability of data. While it is understandable that patient privacy and compliance with GDPR rules might limit data sharing, this could potentially restrict the ability for independent verification of results. It would be beneficial if the data could be made available in a de-identified format to other researchers upon reasonable request. Authors’ response: We have now ensured that all underlying data used in the manuscript will be made freely available from the research repository of Norwegian University of Science and Technology (DataverseNO) under the CC0 (Creative Commons Zero) license. Ethical Compliance: The study's approval by the Regional Committee for Medical and Health Research Ethics of Mid-Norway and adherence to the Declaration of Helsinki are commendable. This ensures that the study meets high ethical standards. Authors’ response: No further comments. Manuscript Presentation: Clarity and Language: The manuscript is well-written and presents the research in a clear and understandable manner. The use of standard English and clear articulation of the research methods and findings makes the manuscript accessible to readers. Authors’ response: No further comments. Competing Interests and Funding: The declaration that there are no competing interests is noted. It's important for maintaining the objectivity of the study. However, information regarding specific funding sources or grants, if any, was not mentioned. Including this information would provide transparency about the potential influences on the research. Authors’ response: We have now included complete information of funding sources in both the PLOS ONE submission system and cover letter. The following text is included under “Funding Statement” in the submission system: This work was supported by several grants. The presented work and also the validation of events from Cohort 1, 2 and 4 was supported by research grants from Nord-Trøndelag Hospital Trust (https://www.hnt.no/om-oss/contact/about-helse-nord-trondelag/) to C.S.R. and H.D., while the validation of events in Cohort 3 was supported by a research grant from SomaLogic (Inc., Boulder, CO, USA; https://somalogic.com/) to M.A.W. (Olson KA, Beatty AL, Heidecker B, Regan MC, Brody EN, Foreman T, et al. Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts. Eur Heart J. 2015;36(48):3426-34. Epub 2015/08/22. doi: 10.1093/eurheartj/ehv385. PubMed PMID: 26294790; PubMed Central PMCID: PMCPMC4685178.). The validation of events from Cohort 5 was funded by research grant to B.O.Å. the Research Council of Norway (grant number 231149/F20; https://www.forskningsradet.no/en/). None of the funders had any role in neither designing the study, collecting or analyzing the data, decision to publish, nor preparation of the manuscript. Recommendations: Data Sharing: Consider providing a more detailed explanation of the data restrictions and potential ways researchers can access the data while still complying with GDPR and privacy concerns. Authors’ response: Please see our reply above. Data will be made freely available from the research repository (DataverseNO) under the CC0 (Creative Commons Zero) license. Sub-Categories Analysis: Further elaboration on the validity of different sub-categories of diagnoses would be beneficial. This could provide deeper insights into which specific types of diagnoses are more or less reliable. Authors’ response: In this manuscript we chose to focus on factors easily extracted from the patient administrative system, and thus, easily available for researchers using cardiovascular diagnoses as clinical endpoints. As shown in the manuscript page 9-10 only a few patients were diagnosed with subcategories available from the patient archive system not included in the analyses, e.g. 11 patients with AMI type 3-5. One important finding was that the specific diagnoses, i.e. including information on subcategories, tended to be more valid than the more general diagnoses. We have now included some information in the limitation section highlighting that further evaluation of subcategories was not performed related to a low number of available diagnoses or information lacking in the patient archive system (page 20, lines 428-9). Future Research Directions: Suggestions for future research, especially on how to improve the validity of diagnoses with lower PPV like TIA, would be beneficial. This could guide subsequent studies in this area. Authors’ response: We agree that further research on how to improve the validity of cardiovascular diagnoses, especially those with low positive predictive values like TIA, would be important. We have included some comments on this topic in the revised manuscript (page 20-21, lines 447-50). Review Comments by Reviewer #2 Excellent article that is very well written. Results are well presented and conclusions including limitations are well discussed. A couple of minor points - One of the limitations is that this study is applicable mainly to the HUNT system and demonstrates the fidelity of their diagnoses. Unsure of the generalizability across other study groups Authors’ response: As shown in the manuscript (page 5, lines 110-2) population 1 and 2 were included outside the HUNT Study, while the larger cohorts 3-5 were identified based on participation in the HUNT Study. However, the participation rate in the different waves of the HUNT Study has been high compared to other population studies. In details: � HUNT1 had 77,212 participants (participation rate 89.4%) � HUNT2 had 65,237 participants (participation rate 69.5%) � HUNT3 had 50,807 participants (participation rate 54.1%) � HUNT4 had 56,078 participants (participation rate 54%) Even though inhabitants not participating in the HUNT Study has been shown to have lower socioeconomic status, higher mortality and higher prevalences of several chronic diseases (Langhammer, et al. BMC Med Res Methodol 2012. Doi: 10.1186/1471-2288-12-143), we have no indication that the participation in the populational study influence the diagnostic procedures in the hospitals. Nevertheless, we believe that the large number of included patients in HUNT studies and the high participation rate reduce the selection bias, and that the presented data are generalisable to others. We have included some comments in the limitation section (page 19, lines 419-21). - As mentioned in the limitation section, ideally all cases should have been reviewed by at least two cardiologists if not more. This does limit the validity of conclusions slightly. Consider a repeat study in the future with better validation if possible Authors’ response: We completely agree that for the best validity of the results all cases should ideally have been reviewed by at least two different clinical experts. However, in line with other similar studies such a strict methodology is not comon as the workload and available resources rarely are matched. The use of different experts for the validation procedures reduces its limitation, but the limitation still exists. We have included a comment in the limitation section of the revised manuscript (page 20, lines 441-2). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0302181.r002
28 Mar 2024 Decision Letter - Vikramaditya Samala Venkata, Editor The influence of diagnostic subgroups, patient- and hospital characteristics for the validity of cardiovascular diagnoses – Data from a Norwegian hospital trus PONE-D-23-36180R1 Dear Dr. Rye, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Vikramaditya Samala Venkata Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: all comments have been addressed. the authors have addressed the comments from the reviewers and this is now ready for acceptance. Reviewer #2: All reviewer comments have be addressed in an acceptable manner and is reported in the manuscript. I recommend this manuscript be approved ****** 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: HARPREET SINGH GREWAL Reviewer #2: Yes: Venkata Buddhavarapu ******** https://doi.org/10.1371/journal.pone.0302181.r003
Formally Accepted
4 Apr 2024 Acceptance Letter - Vikramaditya Samala Venkata, Editor PONE-D-23-36180R1 PLOS ONE Dear Dr. Rye, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Vikramaditya Samala Venkata Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0302181.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .