Risk factors for pulmonary infection in elderly patients with type 2 diabetes: A protocol for systematic review and meta-analysis

Zhaoyang Wei; Wenhao Su; Hairong Jia; Luo Yang; Jiaqi Zhang; Yanru Wang

doi:10.1371/journal.pone.0328355

Peer Review History

Original SubmissionNovember 27, 2024
Decision Letter - Aida Fallahzadeh, Editor PONE-D-24-54675Risk factors for pulmonary infection in elderly patients with type 2 diabetes: a protocol for systematic review and meta-analysisPLOS ONE Dear Dr. Yanru, 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 Mar 01 2025 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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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 Additional Editor Comments: Dear Dr. Yanru, Thank you for your submission of "Risk factors for pulmonary infection in elderly patients with type 2 diabetes: a protocol for systematic review and meta-analysis" to our journal. After careful consideration, I, along with the reviewer, believe that your manuscript has great potential, but there are several important revisions that need to be addressed before it can be accepted for publication. The feedback from the reviewer is attached, and they have identified key areas for improvement. These revisions are substantial but necessary to enhance the overall quality and impact of your paper. Kind regards Aida Fallahzadeh, MD Guest Editor [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Partly ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Partly ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No ****** 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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This manuscript outlines a well-structured protocol for a systematic review and meta-analysis aimed at identifying risk factors for pulmonary infections in elderly patients with type 2 diabetes. The topic is highly relevant and addresses an important gap in the current literature. The authors have followed established guidelines such as PRISMA-P and registered their protocol in PROSPERO, enhancing the credibility and transparency of their study. However, there are areas where the protocol could be improved to ensure methodological rigor and clarity. Below are my detailed comments. Major concerns: Definition of Pulmonary Infection: The inclusion criteria for "diabetes pulmonary infection" are broad. Clarify how heterogeneity in diagnostic criteria (e.g., clinical diagnosis vs. self-report) will be managed. Management of High Heterogeneity: The protocol mentions descriptive analysis if heterogeneity exceeds 75%. Provide more details about how the authors plan to interpret and handle such cases. Exclusion Criteria: The exclusion of conference articles and protocols may omit valuable preliminary findings. Justify this decision or consider including these sources with appropriate caveats. Minor Concerns Subgroup Analysis: While subgroup analyses are planned, specific subgroup categories (e.g., age groups, geographical regions) should be predefined to enhance clarity. GRADE Framework: Expand on how GRADE will be applied, particularly the domains assessed and the thresholds for grading evidence quality. Publication Bias: The "cut-and-patch approach" for publication bias requires further explanation to avoid ambiguity. Pilot Search: A pilot search to validate the feasibility and comprehensiveness of the search strategy would strengthen the protocol. Figures and Appendices: The PRISMA flow diagram (S1 Fig) should be included in the main document for better visibility and understanding. Suggestions for Improvement: Predefine risk factors and subgroup categories in the protocol. Provide a rationale for excluding low-quality studies based on specific score thresholds. Consider including conference articles or gray literature with appropriate quality checks. Add a brief justification for the statistical tools (e.g., RevMan 5.4, STATA 16.0) used for analysis. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". 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Revision 1
26 Jun 2025 Author Response Revised Manuscript with Track Changes We are very grateful for your professional comments on our article. As you are concerned, there are several issues that need to be addressed. Based on your suggestions, we have made extensive corrections to the previous manuscript, and the specific corrections are as follows. Reviewer #1� Definition of Pulmonary Infection: This manuscript outlines a well-structured protocol for a systematic review and meta-analysis aimed at identifying risk factors for pulmonary infections in elderly patients with type 2 diabetes. The topic is highly relevant and addresses an important gap in the current literature. The authors have followed established guidelines such as PRISMA-P and registered their protocol in PROSPERO, enhancing the credibility and transparency of their study. Response�Thanks for the positive comments Major concerns: Definition of Pulmonary Infection: The inclusion criteria for "diabetes pulmonary infection" are broad. Clarify how heterogeneity in diagnostic criteria (e.g., clinical diagnosis vs. self-report) will be managed. Response�Thank you for your valuable comments. We have carefully searched the relevant literature and further clarified the diagnostic criteria and definition of diabetes combined with pneumonia. At the same time, in order to standardize the heterogeneity of diagnostic criteria, we require that the patient's diagnosis must be based on some objective examination results. We have carefully revised the revised manuscript based on your comments. This study was based on the Chinese Consensus for the Diagnosis and Treatment of Diabetes Complicated with Pneumonia. Patients with confirmed diabetes-related pulmonary infections through clinical diagnosis or self-reporting were included. To standardize the management of heterogeneity in diagnostic criteria, we required that the diagnostic basis of the patients must include: 1. Fasting blood glucose ≥ 7.0 mmol/L or random blood glucose ≥ 11.1 mmol/L and confirmed pulmonary infection by CT; 2. The clinical case needs to include CURB-65 score, inflammatory markers, and qualified pathogen evidence. Please refer to the "Participants" section. Management of High Heterogeneity: The protocol mentions descriptive analysis if heterogeneity exceeds 75%. Provide more details about how the authors plan to interpret and handle such cases. Response�We think this is a good suggestion. We have improved the solution for handling high heterogeneity in the revised manuscript. If the heterogeneity exceeds 75%, we will explore the source of heterogeneity through subgroup analysis (according to study design, population characteristics, etc.). If the heterogeneity still cannot be eliminated, no meta-analysis will be performed. We will use descriptive analysis. If heterogeneity exceeds 75%,We will conduct subgroup analyses (based on study design, population characteristics, etc.) to explore the sources of heterogeneity. If the heterogeneity still cannot be eliminated,a meta-analysis will not be performed. We shall employ descriptive analysis. Please refer to the "Strategy for Data Synthesis" section. Exclusion Criteria: The exclusion of conference articles and protocols may omit valuable preliminary findings. Justify this decision or consider including these sources with appropriate caveats. Response�We thank the reviewers for their valuable comments. This study chose to exclude conference abstracts and research plans based on the following considerations: Methodological rigor requirements: 1.Conference abstracts often lack complete methodological details and original data, making it difficult to conduct quality assessments (such as NOS/AHRQ scores), which may introduce bias risks. The research protocol is prospectively designed and has not yet produced analyzable research results. 2.Matching of evidence levels: According to the GRADE system, conference literature is classified as "low-level evidence", which is different from the "at least moderate-quality evidence" required by the research objectives. Retaining such literature may reduce the overall strength of evidence. Minor Concerns Subgroup Analysis: While subgroup analyses are planned, specific subgroup categories (e.g., age groups, geographical regions) should be predefined to enhance clarity. Response�We appreciate your reminder and we have added the specific subgroup analysis categories in the revised manuscript. If heterogeneity exceeds 75%,We will conduct subgroup analyses (based on study design, population characteristics, etc.) to explore the sources of heterogeneity. If the heterogeneity still cannot be eliminated,a meta-analysis will not be performed. We shall employ descriptive analysis. Through subgroup analysis(According to the research design, population characteristics, etc.) or sensitivity analysis, the analysis will be conducted. If the heterogeneity exceeds 75%, meta-analysis will not be performed. Please refer to the "Sensitivity Analysis" and "Strategy for Data Synthesis" GRADE Framework: Expand on how GRADE will be applied, particularly the domains assessed and the thresholds for grading evidence quality. Response:We thank the reviewer for drawing our attention to this issue. We have systematically supplemented the application of the GRADE method in the revised manuscript, which mainly includes the following key contents: 1. The grading of the GRADE system assessment quality; 2. The GRADE scoring criteria; 3. A detailed description of how to use the GRADE system to assess the quality of evidence. Two researchers (WH and HR) will use the GRADE system to assess the quality of evidence, grading it based on five dimensions: risk of bias, inconsistency, indirectness, imprecision, and publication bias. The initial rating for randomized controlled trials is high quality, while observational studies are rated as low quality. The grades will be dynamically adjusted based on the assessment results of each dimension: when there is severe bias (such as methodological flaws), significant heterogeneity (I² ≥ 75%), deviation of PICO elements, confidence intervals crossing clinical thresholds, or publication bias, the grade will be downgraded; when a large effect size (RR > 2/< 0.5) or dose-response relationship is found, the grade will be upgraded. For the assessment of publication bias, when the number of included studies is more than 10, the Egger test (p < 0.05 indicates the presence of bias) is used. If p > 0.05, the trim-and-fill method is employed to iteratively prune asymmetric extreme values, estimate missing studies, and recalculate the effect size to correct potential publication bias. The final evidence quality is classified into four levels: high, medium, low, and very low, corresponding to different recommendation intensities. In the heterogeneity test, when I2 is less than 50% and P is greater than 0.05, it indicates a relatively small degree of heterogeneity, and the fixed-effect model can be used for analysis; conversely, when I2 is greater than or equal to 50% and P is less than or equal to 0.05, it indicates the presence of heterogeneity. If after eliminating obvious clinical heterogeneity factors, the heterogeneity is still greater than or equal to 50%, then the random-effect model should be used for analysis. For significant heterogeneity, we will use Stata 16.0 software for testing, focusing on age, gender, region, sample size, and various risk factors. Through subgroup analysis(According to the research design, population characteristics, etc.) or sensitivity analysis, the analysis will be conducted. If the heterogeneity exceeds 75%, meta-analysis will not be performed. We will use descriptive analysis. The funnel plot and Egger test (α = 0.1) will be used to evaluate publication bias. Please refer to the "Quality of evidence and publication biases assessment" and "Sensitivity analysis" Publication Bias: The "cut-and-patch approach" for publication bias requires further explanation to avoid ambiguity. Response: We thank the reviewer for the suggestion. We have added the “deletion and repair method” explanation of publication bias in the revised manuscript to avoid ambiguity. Two researchers (WH and HR) will use the GRADE system to assess the quality of evidence, grading it based on five dimensions: risk of bias, inconsistency, indirectness, imprecision, and publication bias. The initial rating for randomized controlled trials is high quality, while observational studies are rated as low quality. The grades will be dynamically adjusted based on the assessment results of each dimension: when there is severe bias (such as methodological flaws), significant heterogeneity (I² ≥ 75%), deviation of PICO elements, confidence intervals crossing clinical thresholds, or publication bias, the grade will be downgraded; when a large effect size (RR > 2/< 0.5) or dose-response relationship is found, the grade will be upgraded. For the assessment of publication bias, when the number of included studies is more than 10, the Egger test (p < 0.05 indicates the presence of bias) is used. If p > 0.05, the trim-and-fill method is employed to iteratively prune asymmetric extreme values, estimate missing studies, and recalculate the effect size to correct potential publication bias. The final evidence quality is classified into four levels: high, medium, low, and very low, corresponding to different recommendation intensities. Please refer to the Quality of evidence and publication biases assessment Pilot Search: A pilot search to validate the feasibility and comprehensiveness of the search strategy would strengthen the protocol. Response: Thank you for your careful review of the research methods. Regarding the suggestions for preliminary search, we have carefully considered that as a research protocol, the current version already contains a pre-tested search strategy (Supplementary File), and considering that the core purpose of the protocol is to preset the method framework rather than to verify, its effectiveness will be fully presented through the PRISMA flow chart of the formal systematic review stage. Figures and Appendices: The PRISMA flow diagram (S1 Fig) should be included in the main document for better visibility and understanding. Response: Thank you for the reviewer's detailed comments. We have included the PRISMA flow diagram (S1 Fig) in the main text of the revised manuscript. Cover Letter Dear editor� On behalf of all the authors involved in the writing of the article titled "Risk Factors for Pulmonary Infections in Elderly Patients with Type 2 Diabetes: Systematic Review and Meta-analysis Protocol" (PONE-D-24-54675), I would like to express my sincere gratitude to you and the reviewers for your valuable comments and constructive suggestions. I have carefully considered these comments and have revised the paper based on their opinions. These comments are extremely valuable and helpful for us to improve this article. We have made numerous revisions to the manuscript according to the editors' and reviewers' opinions. We hope these revisions will be satisfactory. During this revision process, based on the actual contributions of each author, after all-party consensus, we adjusted the author order. Wei Chaoyang's position was moved forward because he made significant contributions to this revised paper. Once again, we thank you for considering publishing our paper in your journal. We look forward to receiving your reply as soon as possible. Best wishes� Sincerely, Wang Yanru Zhejiang Chinese Medical University Wangyanru001@outlook.com June 24th, 2025 https://doi.org/10.1371/journal.pone.0328355.r002
Decision Letter - Aida Fallahzadeh, Editor Risk factors for pulmonary infection in elderly patients with type 2 diabetes: a protocol for systematic review and meta-analysis PONE-D-24-54675R1 Dear Dr. Wang, 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, Aida Fallahzadeh Guest Editor PLOS ONE Additional Editor Comments (optional): Dear Authors, Thank you for thoroughly addressing all the comments raised during the review process. I found your responses clear and satisfactory. I am pleased to inform you that the manuscript has been accepted for publication. Bests, Aida Fallahzadeh, MD Guest Editor Reviewers' comments: https://doi.org/10.1371/journal.pone.0328355.r003
Formally Accepted
Acceptance Letter - Aida Fallahzadeh, Editor PONE-D-24-54675R1 PLOS ONE Dear Dr. Wang, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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. Aida Fallahzadeh Guest Editor PLOS ONE https://doi.org/10.1371/journal.pone.0328355.r004

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