PONE-D-24-57142Association of healthcare fragmentation and overall survival in patients with kidney transplant in ColombiaPLOS ONE

Dear Dr. Buitrago,

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.

While the introduction refers to healthcare fragmentation in general terms, it lacks sufficient contextualization regarding how fragmentation specifically affects kidney transplant patients in Colombia. I recommend expanding this section to clarify why Colombia is an appropriate setting for studying healthcare fragmentation and how particular features of its healthcare system contribute to this issue. Strengthening the introduction in this way would enhance the overall framing of the study.

Clearly define what is meant by “fragmentation” within the context of this research. It is essential to specify how fragmentation is conceptualized and measured, and to elaborate on the mechanisms through which it impacts the Colombian healthcare system, particularly for kidney transplant recipients.

The discussion section should be strengthened. I suggest analyzing how the study’s findings compare or contrast with those reported in other countries. This comparative approach would better highlight the study's contribution to the global literature on healthcare fragmentation and transplant outcomes.

Improve the conclusion to make it more assertive and impactful. It should not only summarize the key findings, but also clearly articulate the implications for policy, practice, and future research.

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PLOS ONE

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Reviewers' comments:

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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: Partly

Reviewer #3: Yes

Reviewer #4: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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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: Association of healthcare fragmentation and overall survival in patients with kidney transplant in Colombia

Title

• Make the title more engaging and reflective of the results. For example:

"Impact of Healthcare Fragmentation on Three-Year Survival of Kidney Transplant Recipients in Colombia."

Abstract

• The abstract does not mention why healthcare fragmentation is a significant issue in Colombia or LMICs. Add a sentence explaining why fragmentation is relevant in Colombia or LMICs.

• The conclusion is clear but repetitive with the introduction. Streamline the conclusion to avoid repetition. Focus on the implications and recommendations.

Introduction

• While the introduction mentions healthcare fragmentation in general, it does not provide enough context about how fragmentation specifically impacts kidney transplant patients in Colombia. Expand on why Colombia is a relevant setting for studying fragmentation and how its healthcare system's structure creates challenges.

• The phrase "fragmentation manifests both horizontally... and vertically" could be explained more clearly for a general audience.

Methods

• The definition of healthcare fragmentation ("measured by the number of different healthcare providers") is too simplistic and lacks methodological depth. Provide more detail on how fragmentation was quantified.

• The rationale for selecting the 75th percentile as the cut-off for high fragmentation is not explained. Justify the use of the 75th percentile for defining high fragmentation.

Results

• Descriptions of geographical fragmentation are overly detailed, making it difficult to identify key findings. Focus on the most important findings and present them concisely. Focus on the most important findings and present them concisely. For example: "Patients with high fragmentation (≥11 providers) had a significantly higher mortality rate (18%) compared to those with low fragmentation (12%) (p=0.04)."

• Some results, such as "high fragmentation was associated with a 49% increased mortality risk," are presented without interpretation or context. Briefly explain the implications of key results, e.g.: "This suggests that greater provider involvement, without effective care coordination, negatively impacts patient outcomes."

• Some terms (e.g., "fragmentación") appear in Spanish (Table 1), which is inconsistent with the rest of the English manuscript. Standardize the language to ensure all terms are in English.

Discussion

• Some statements, such as "fragmentation leads to poor outcomes," are too broad and not linked directly to the study findings. Link findings more explicitly to practical implications.

• The discussion does not sufficiently address how the findings can be used to inform healthcare policies or improve care coordination in Colombia. Discuss how the findings align or differ from those in other countries to emphasize the study's contribution to global literature.

• The study could benefit from comparing findings with fragmentation studies in high-income countries to provide a broader context. Avoid overly general statements by linking each claim to specific results from the study.

Conclusion

• The conclusion restates key findings but could be more impactful. Focus on actionable recommendations for reducing fragmentation and improving patient outcomes. For example: "Our findings highlight the urgent need to implement integrated care models and enhance care coordination to reduce mortality risks in kidney transplant patients. Policymakers should prioritise strategies to streamline healthcare delivery, particularly in fragmented systems like Colombia."

Reviewer #2: I appreciate your hard work.

Financial Disclosure:

In the "Financial Disclosure" section of PLOS One Submission System, part please add where the partial funders played specific roles, like- Study design, Data collection and analysis, Decision to publish or Preparing the manuscript. If the funders have no role you can simply write it as, "The funders did not contribute in study design, fieldwork, data analysis, decision to publish or preparation of the manuscript." But if they do, please mention in which specific sector they contributed.

Introduction:

As per your statement, "To our knowledge, no studies have specifically evaluated the association between healthcare fragmentation and survival outcomes in renal transplant recipients in low- and middle-income countries (LMICs)." So, while you have mentioned that we don't have data in LMICs, but is there any in HICs? please look for the available studies on similar studies conducted in High Income Countries so that a contrast can be build up in Discussion section. If there is no studies available in HICs you can mention it. That will give stronger rationale for the study.

Result:

Deeper analysis and findings are illustrated with well structured and readable figures and tables.

Discussion:

As mentioned, please find some existing studies conducted in High Income Setting so that this study can compare and contrast key features and increase its strength.

Acknowledgement:

Kindly remove the funding source in the "Acknowledgments" or anywhere else in the manuscript file. Funding information should only be entered in the "financial disclosure" section of the submission system as mentioned earlier in the review.

Reviewer #3: Introduction

• The introduction provides context on healthcare fragmentation and why it is an important issue.

• The literature review is relevant and establishes the need for the study.

Methods

• The study design is appropriate for the research question.

• Ethical considerations are mentioned (if applicable).

Results

• The results are well-structured and follow a logical order.

• Use of tables and figures helps in presenting data effectively.

Discussion

• The discussion links findings to the broader literature.

• The practical implications of the results are explored.

6. Conclusion

Strengths:

• Summarizes key findings effectively.

Reviewer #4: This study explores the link between healthcare fragmentation during the first year after kidney transplantation and three-year mortality risk in Colombia. The analysis of national administrative data revealed that higher fragmentation significantly increases mortality risk, even when adjusting for age, gender, region, comorbidities, and transplant year, with a 49% higher risk for those experiencing high fragmentation.

Building on the teams' prior research, this study highlights the importance of care coordination for chronic disease patients. Its findings are especially relevant for low- and middle-income countries (LMICs), where healthcare systems tend to be fragmented and under-resourced.

Strengths:

The manuscript is clearly structured and written with clarity.

The use of a national database enhances the study’s generalizability and policy relevance.

The findings are communicated in an accessible manner, with appropriate use of tables and figures.

Weaknesses:

The arguments could be better situated within the existing literature, especially regarding kidney transplantation and healthcare fragmentation in comparable contexts.

Overall Recommendation:

This is a well-written and policy-relevant manuscript addressing a significant public health issue. I recommend acceptance pending revision of the points below.

Major Issues

Methods

Lines 148–150- The authors should elaborate on how fragmentation scores were derived from the database. Were they based on the specific services provided? How are services that require multiple health workers accounted for? Although the authors have referenced previous studies that used this measure, further information is necessary to clarify its validity for their current research.

Lines 154-155- More detail is needed regarding Colombia’s insurance system and how the geographic regions were categorized. Also more information on the Charlson Comorbidity Index (CCI) is important for the general audience, a brief description of how it is calculated, what conditions it includes, and its relevance to transplant populations would enhance clarity, especially for readers outside the clinical field.

Results

Table 2- Each region should have its own unique subscript, such as "a," "b," and "c," with explanations in the footnotes as before. Bogotá, D.C. should be labeled as "Metropolitan" if more than one region is combined here (it seems so).

Discussion

Line 261-267- The authors compare their findings to research on other chronic conditions. However, the management and care coordination needs of kidney transplant patients differ substantially from those with cancers for example. The argument would be more persuasive if supported by literature on kidney transplantation, As the authors mentioned that their work is the first in LMICs, it is important to consider findings related to kidney transplants from non-LMICs. Comparing their results with studies specifically focused on kidney transplants could provide valuable context. The cited study may not be sufficient to align their findings with existing literature. This is a crucial point that needs to be addressed.

Line 267-270- The manuscript references general issues with fragmentation in other countries but lacks detail about Colombia’s healthcare system. Are delays in treatment, duplicative services, and poor care coordination documented problems locally?

Limitations- The authors noted key limitations in their study related to clinical information important for patient survival. However, they did not specify details that could confound or interact with their results. this information is for the study's conclusion.

References- Reference 13 appears to be already published, and the DOI provided is incorrect. The same article seems to be cited again as Reference 15. Please verify and adjust accordingly.

Minor Issues

Line 79–81: A citation is needed to support the description of Colombia’s healthcare system.

Lines 81–86: Important claims are made to justify the research question, but no supporting literature is cited.

Line 89–90: Citing similar studies from high-income countries would strengthen the rationale for the study.

Line 104–106: It is unclear whether the study truly addresses all the claims made in this paragraph.

Line 169–170: I suggest including the global test p-value from the Schoenfeld residuals.

Line 173: Consider adding a STROBE checklist as supplementary material.

Lines 179–181: These participant exclusion criteria should be moved to the Methods section. The rationale for excluding individuals <18 years should be stated. If this is due to different survival patterns, why not also consider an upper age limit (e.g., >75)?

Table 1: Clarify “Mean of different healthcare; X (SD)” in a footnote, please also, explain what is meant by “other department” under the region variable.

Table 2: Same labeling issues as noted above. Ensure clarity in regional categories.

Table 3 and 4: Statistically significant values should be marked (e.g., using asterisks or bold text) for easier interpretation.

Results – Were there significant differences in unadjusted models? If so, consider including or mentioning these results.

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Reviewer #1: Yes:  Faizul Akmal Abdul Rahim

Reviewer #2: Yes:  Rehnuma Abdullah

Reviewer #3: Yes:  Abdulmalik Alilu Abubakar

Reviewer #4: No

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Association of Healthcare Fragmentation with Three-Year Survival among Kidney Transplant Recipients in Colombia

PONE-D-24-57142R1

Dear Dr. Giancarlo Buitrago,

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.

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Kind regards,

Oriana Rivera-Lozada de Bonilla

Academic Editor

PLOS ONE

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 #5: All comments have been addressed

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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 #5: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #5: Yes

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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 #5: Yes

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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 #5: Yes

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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 #5: The revised manuscript is substantially improved and demonstrates a high level of scientific rigor, clarity, and relevance. The authors have thoroughly and thoughtfully addressed all comments from the previous review round. Specifically:

The title and abstract have been appropriately refined to avoid causal language while improving clarity and relevance.

The methodology is now clearly described, with a well-justified fragmentation metric, robust covariate adjustment, and verification of proportional hazards assumptions using Schoenfeld residuals.

The results are well-structured and statistically rigorous, with both unadjusted and adjusted findings presented transparently.

The discussion has been strengthened by including comparisons with high-income country literature and better linking findings to practical healthcare and policy implications.

Language use throughout the manuscript is clear, consistent, and adheres to standard academic English.

Data availability, ethical approval, and formatting are all fully compliant with journal requirements.

Overall, the study offers valuable insights into the impact of healthcare fragmentation on kidney transplant survival in LMIC settings and represents a meaningful contribution to the literature on health system performance and transplant outcomes.

I have no further concerns and recommend acceptance.

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Reviewer #5: Yes:  Ibrahim A. Abdulganiyyu PhD

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