The relationship between conference presentations and in-hospital mortality in patients admitted with acute myocardial infarction: A retrospective analysis using a Japanese administrative database

Daisuke Takada; Yuki Kataoka; Tetsuji Morishita; Noriko Sasaki; Susumu Kunisawa; Yuichi Imanaka

doi:10.1371/journal.pone.0315217

Peer Review History

Original SubmissionSeptember 10, 2024
22 Oct 2024 Decision Letter - Shukri AlSaif, Editor PONE-D-24-39413The Relation between Conference Presentations and In-hospital Mortality in Patients Admitted with Acute Myocardial Infarction: A Retrospective Analysis Using a Japanese Administrative DatabasePLOS ONE Dear Dr. Imanaka, 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 Dec 06 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. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this study, the authors demonstrated the association between conference presentations and in-hospital mortality in patients with myocardial infarction using a Japanese administrative database. While the research topic is of significant interest, there are several points that should be improved for better understanding. Please see the following comments to the authors. Major comments Abstract 1. The font size in the abstract is inconsistent with the rest of the manuscript. Please ensure that the font size is uniform throughout the document. 2. The hypothesis of this study is not explicitly stated in the abstract. Clearly stating the study hypothesis will help readers understand the rationale behind the research. Methods 1. The section titled "Intervention" may not be the most appropriate terminology in this context. The term "Exposure" might be more fitting, considering the nature of the study. Please revise accordingly. 2. The Ethical Consideration and Data Availability sections contain overlapping information with the previous sections. To improve clarity and avoid redundancy, please condense or reorganize these sections. 3. It is unclear what specific information was collected from the database. A more detailed description of the type and scope of the collected data is needed for transparency. 4. The authors should consider including additional variables for adjustment, particularly ADL prior to hospitalization, NYHA classification, and the presence of pulmonary disease. These are important confounding factors that could impact the study's findings. 5. The authors used multivariable logistic regression analysis; however, given that both individual-level and hospital-level factors are being examined, a multi-level analysis may be more suitable. Please clarify whether a multi-level analysis was conducted. If not, the authors should provide a rationale for this choice. 6. Please consider adding hospital variables such as whether the hospitals are university-affiliated or their geographical location. 7. The handling of readmissions in the analysis is unclear. Please provide details on how readmission data was managed and its potential impact on the study outcomes. 8. Please clarify if there is any relationship between the number of conference presentations and in-hospital mortality, as this could provide additional insights into the factors affecting patient outcomes. Other comments 1. Proof-reading is required to address several grammatical and stylistic issues throughout the manuscript. ****** 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? 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Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0315217.r001
Revision 1
5 Nov 2024 Author Response Response to the Reviewers Major comments Abstract 1. The font size in the abstract is inconsistent with the rest of the manuscript. Please ensure that the font size is uniform throughout the document. Thank you for pointing this out, and sorry for the inconsistent font size. We have revised font sizes to ensure consistency throughout the document. 2. The hypothesis of this study is not explicitly stated in the abstract. Clearly stating the study hypothesis will help readers understand the rationale behind the research. Thank you for your suggestion. We have clearly stated our hypothesis in the abstract and introduction. Abstract(P3 L31-35): ”Background and aims: Clinicians’ research activities reportedly improve their healthcare performance. Presenting research at conferences may be related to improved patient care outcomes; however, few studies have investigated this relationship. Thus, we examined the association between presenting at conferences and the mortality of patients hospitalized for acute myocardial infarction..” Introduction(P7 L90-95): “Our hypothesis is that clinicians’ conference presentations might be associated with improved patient outcomes through increased evidence-based practice. Therefore, we examined the association between clinicians’ conference presentations and mortality in acute myocardial infarction (AMI) cases after adjusting for potentially confounding patient characteristics. We further confirmed that the proportions of prescribed medical therapies were optimal according to treatment guidelines for evidence-based practice.” Methods 1. The section titled "Intervention" may not be the most appropriate terminology in this context. The term "Exposure" might be more fitting, considering the nature of the study. Please revise accordingly. Thank you for your suggestion. In our manuscript, we have changed the term to “Exposure.” (P9 L119) 2. The Ethical Consideration and Data Availability sections contain overlapping information with the previous sections. To improve clarity and avoid redundancy, please condense or reorganize these sections. Thank you for pointing this out, and we apologize for the overlapping information. We have revised the manuscript. (P11 L159 - P12 L164 ) “Ethical consideration and Data availability The Ethics Committee, Graduate School of Medicine, Kyoto University, approved this study (approval number: R0135). This study was conducted in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects of the Ministry of Health, Labour and Welfare, Japan. These guidelines require the protection of patient anonymity. The data were anonymized, and the requirement for informed consent was waived.” 3. It is unclear what specific information was collected from the database. A more detailed description of the type and scope of the collected data is needed for transparency. Thank you for your suggestion. We have added more details about the data we collected. (P8 L104 - 111) “The DPC data comprises a Form 1, an EF-file, and other files. Form 1 contains important clinical summaries, including date of birth, sex, admission dates, discharge outcome, diagnosis, surgical procedure, and various severity scores such as the Killip classification upon admission and other clinical information. The International Classification of Diseases, 10th Revision (ICD-10) codes were used for diagnosis in the DPC database. The EF-file contains information on medical resource utilization during hospitalization, including medications administered and other medical procedures.” 4. The authors should consider including additional variables for adjustment, particularly ADL prior to hospitalization, NYHA classification, and the presence of pulmonary disease. These are important confounding factors that could impact the study's findings. Thank you for your suggestion about the additional variables for adjustment. We had chosen the confounding factors that refer to past reports and clinical experience as physicians (some authors), but we considered the additional variables again and added several variables as outlined below. ・The presence of pulmonary disease: We added chronic obstructive pulmonary disease as a key pulmonary comorbidity based on the Charlson Comorbidity Index (1-3). Method(P10 L136-139): “Model 1 was adjusted for sex, age, the Killip classification, smoking, ambulance use, hypertension, atrial fibrillation, old myocardial infarction, diabetes, renal disease and chronic obstructive pulmonary disease (personal factors)” ・Patient ADL data were often missing from the database, so we performed the analysis using the ADL variable in the sensitivity analysis. Method(P11 L148-150): “4) additionally adjusting for the Barthel index when the data did not contain any missing measurements ” Result(P16 L218-219): “4) excluding 9,802 patients without the Barthel index, then adjusting for the Barthel index: OR=0.78, 95% CIs: 0.72 to 0.85.” ・NYHA classifications would be included in the database if the patients were diagnosed with heart failure and the most resources were spent on heart failure treatment during hospitalization. However, because heart failure was not the primary diagnosis in this analysis, the NYHA classifications were rarely included in the research data; hence, we cannot adjust the NYHA classification variable in the revised manuscript. We have added this as a limitation in the revised manuscript, as outlined below. Discussion(P20 L280 - P21 L284):“Second, unmeasured confounding hospital and personal factors exist, such as organizational culture, the cardiologist’s motivation, and NYHA classification. Future observational studies with comprehensive measurements of these confounding factors would enhance our understanding of their effects on patient mortality.” 5. The authors used multivariable logistic regression analysis; however, given that both individual-level and hospital-level factors are being examined, a multi-level analysis may be more suitable. Please clarify whether a multi-level analysis was conducted. If not, the authors should provide a rationale for this choice. Thank you for your suggestion. We conducted a multilevel analysis and provide the results (Model 3) in our manuscript. Method (P10 L141 - 142): “Model 3 was a multilevel analysis clustered by hospital codes and adjusted for the same variables as Model 1.” Result (P15 L199): “OR=0.84, 95% CIs: 0.76 to 0.92 in Model 3;” Table 2 (P15 L202 – P16 L211): Odds ratio 95% CI C-statistics Crude 0.68 0.65 to 0.72 0.55 (0.54 to 0.55) Model 1 a 0.73 0.68 to 0.79 0.91 (0.91 to 0.92) Model 2 b 0.76 0.70 to 0.82 0.91 (0.91 to 0.92) Model 3 c 0.84 0.76 to 0.92 - Model 4 d 1.00 0.92 to 1.09 0.94 (0.94 to 0.94) a: Model 1: adjusted for sex, age, Killip classification, smoking, ambulance use, hypertension, atrial fibrillation, old myocardial infarction, diabetes, renal disease, and chronic obstructive pulmonary disease b: Model 2: adjusted for Model 1 plus admission year and the number of patients c: Model 3: multilevel analysis clustered by hospital codes adjusted for the same variables as Model 1 d: Model 4: adjusted for Model 1 plus the evidence-based practices as causal mediation analysis 6. Please consider adding hospital variables such as whether the hospitals are university-affiliated or their geographical location. Thank you for your suggestion. As you say, clinicians from university-affiliated hospitals may affect the results of this research because we think that they may have given presentations about basic research. Therefore, we excluded the university-affiliated hospitals in the sensitivity analysis and confirmed that the results were similar to that of the main analysis. Result(P16 L215): “1) excluding university hospitals and their affiliated hospitals: OR=0.76, 95% CIs: 0.70 to 0.82;)” In contrast, it was difficult to adjust our models for geographical location. We consider the results of Model 3 (a multilevel analysis clustered by hospital codes) to show the results adjusted by alternative hospital variables to some extent. Table 2 (P15 L202 – P16 L211): Odds ratio 95% CI C-statistics Crude 0.68 0.65 to 0.72 0.55 (0.54 to 0.55) Model 1 a 0.73 0.68 to 0.79 0.91 (0.91 to 0.92) Model 2 b 0.76 0.70 to 0.82 0.91 (0.91 to 0.92) Model 3 c 0.84 0.76 to 0.92 - Model 4 d 1.00 0.92 to 1.09 0.94 (0.94 to 0.94) a: Model 1: adjusted for sex, age, Killip classification, smoking, ambulance use, hypertension, atrial fibrillation, old myocardial infarction, diabetes, renal disease, and chronic obstructive pulmonary disease b: Model 2: adjusted for Model 1 plus admission year and the number of patients c: Model 3: multilevel analysis clustered by hospital codes adjusted for the same variables as Model 1 d: Model 4: adjusted for Model 1 plus the evidence-based practices as causal mediation analysis 7. The handling of readmissions in the analysis is unclear. Please provide details on how readmission data was managed and its potential impact on the study outcomes. Thank you for your suggestion. If you mean the readmission data leading to the potential impact denoted in the intra-individual correlation, we considered that the results of the multilevel analysis clustered by hospital codes (Model 3) also showed the results adjusted by alternative hospital variables to some extent. Moreover, when we limited our analysis to only the first hospitalization during the observation period, the odds ratio was 0.76 (0.71–0.80), which was similar to the results of Model 2. We added this result of the sensitivity analysis to the manuscript. Method(P11 L150-151): 5) excluding patients who were readmitted during the observation period . Result(P16 L219 – P17 L220): 5) excluding 871 patients readmitted during the observation period: OR=0.76, 95% CIs: 0.71 to 0.80. 8. Please clarify if there is any relationship between the number of conference presentations and in-hospital mortality, as this could provide additional insights into the factors affecting patient outcomes. To provide additional insights into the causal relationship, we have now performed two further analyses: Causal Mediation Analysis and Generalized Additive Modeling (spline). First, Causal Mediation Analysis (Model 4 in our revised manuscript) showed that clinicians’ conference presentations affected patient outcomes through evidence-based practice, evidenced by the odds ratios being significantly lower in Model 1 but not in Model 4. Method(P10 L142-143): Model 4 was adjusted for Model 1 plus the evidence-based practices through causal mediation analysis. Result(P15 L199 – L200): OR=0.96, 95% CIs: 0.88 to 1.05 in Model 4 Table 2 (P15 L202 – P16 L211): Odds ratio 95% CI C-statistics Crude 0.68 0.65 to 0.72 0.55 (0.54 to 0.55) Model 1 a 0.73 0.68 to 0.79 0.91 (0.91 to 0.92) Model 2 b 0.76 0.70 to 0.82 0.91 (0.91 to 0.92) Model 3 c 0.84 0.76 to 0.92 - Model 4 d 1.00 0.92 to 1.09 0.94 (0.94 to 0.94) a: Model 1: adjusted for sex, age, Killip classification, smoking, ambulance use, hypertension, atrial fibrillation, old myocardial infarction, diabetes, renal disease, and chronic obstructive pulmonary disease b: Model 2: adjusted for Model 1 plus admission year and the number of patients c: Model 3: multilevel analysis clustered by hospital codes adjusted for the same variables as Model 1 d: Model 4: adjusted for Model 1 plus the evidence-based practices as causal mediation analysis Second, Generalized Additive Modeling (spline) revealed the volume-outcome relationship between the number of presentations per year (horizontal axis value) and patient mortality (below). We can graphically depict the causal relationship, but it is difficult to interpret the value of the vertical axis clinically, so we have not included this figure in the revised manuscript. If the editor and reviewers request these outcomes be included in the revised manuscript, we will include them. Other comments 1. Proof-reading is required to address several grammatical and stylistic issues throughout the manuscript. We thank Cambridge English Correction Service (https://cambridge-correction.com) for English language editing, and we have rechecked English grammar and the logical flow of information in the revised manuscript. Reference 1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. 2. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. American journal of epidemiology. 2011;173(6):676-82. 3. Hautamäki M, Lyytikäinen LP, Mahdiani S, Eskola M, Lehtimäki T, Nikus K, et al. The association between charlson comorbidity index and mortality in acute coronary syndrome - the MADDEC study. Scand Cardiovasc J. 2020;54(3):146-52. Attachments Attachment Submitted filename: Response_to_the_Reviewers_1105.docx https://doi.org/10.1371/journal.pone.0315217.r002
22 Nov 2024 Decision Letter - Shukri AlSaif, Editor The Relation between Conference Presentations and In-hospital Mortality in Patients Admitted with Acute Myocardial Infarction: A Retrospective Analysis Using a Japanese Administrative Database PONE-D-24-39413R1 Dear Dr. Imanaka, 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, Shukri AlSaif 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 ******** 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: The authors have adequately revised the manuscript according to the reviewers' recommendations. This version of the manuscript seems suitable for publication. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No ******** https://doi.org/10.1371/journal.pone.0315217.r003
Formally Accepted
28 Nov 2024 Acceptance Letter - Shukri AlSaif, Editor PONE-D-24-39413R1 PLOS ONE Dear Dr. Imanaka, 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. Shukri AlSaif Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0315217.r004

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