Quality of Life and Financial Burden in Duchenne Muscular Dystrophy in Greece: Insights into Health System Performance in the Post-Pandemic Context

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

Major Comments

1. Abstract
   The structured abstract (Background, Methods, Results, Conclusions) is appropriate for Healthcare. However, it remains too long and overly descriptive. The authors should streamline each section to highlight the study’s aims, methodology, principal findings, and implications clearly. Avoid redundant or narrative-style explanations.

2. Introduction
   The introduction provides a comprehensive overview of DMD and related health policy issues but lacks focus. It should end with a clear rationale, research questions, and objectives tailored to the Greek health system. Several paragraphs discuss global frameworks in excessive detail; these could be summarized to improve flow.

3. Methods
   The design and use of validated instruments (e.g., HRQoL questionnaires) are appropriate. However, more transparency is needed regarding:

   • Sampling (number and location of centers, recruitment procedures).

   • Representativeness and justification of the sample size.

   • Handling of missing data or incomplete responses.

   • Whether ethical approval and informed consent were obtained (as required by Healthcare ethics policy).
     The statistical approach, based mainly on descriptive and bivariate analyses, is adequate for an exploratory study, but its limitations should be explicitly acknowledged.

4. Results
   The results are comprehensive but too detailed and sometimes repetitive. The narrative should emphasize key findings linking financial burden to HRQoL outcomes instead of restating all descriptive figures. Tables are clear but dense—consider consolidating or moving supplementary data to appendices. Figures should be reformatted with higher resolution (≥600 dpi) and concise legends.

5. Discussion
   The discussion section demonstrates wide knowledge of the literature but lacks synthesis. It should focus on:

   • How the findings contribute to understanding financial and psychosocial challenges in DMD.

   • Comparison with prior European or Mediterranean studies.

   • The implications for policy and family support programs.
     At present, the section includes repetitive summaries and tangential commentary that obscure the central argument.

6. Conclusions
   The conclusions are relevant but still too general. The authors should link them directly to the data and clearly state limitations, including the small sample, regional scope, and cross-sectional design.

7. Language and Style
   The manuscript requires moderate to major English editing. Grammar, syntax, and article use are inconsistent. Phrases such as “this investigation have two main research questions” or “to build effective education campaigns” need correction. Sentences should be shortened and written in formal, academic tone.

8. Formatting and References

   • Ensure that figures and tables appear in order and are referenced correctly.

   • Check that all acronyms are defined at first use (HRQoL, ICC, etc.).

   • Verify that references conform to MDPI style (numbered citations in brackets, proper capitalization, DOIs included)

9. Consider adding a short paragraph in the Methods describing the questionnaires’ validation in Greek populations.

10. Clarify whether any socioeconomic differences between urban and rural respondents were observed.

11. Ensure the Funding, Ethics, and Data Availability statements follow MDPI format.

Author Response

Response to Reviewer 1 Comments

Major Comments

Comment 1: Abstract. The structured abstract (Background, Methods, Results, Conclusions) is appropriate for Healthcare. However, it remains too long and overly descriptive. The authors should streamline each section to highlight the study’s aims, methodology, principal findings, and implications clearly. Avoid redundant or narrative-style explanations.

Response 1: We thank the reviewer for this helpful comment. The abstract has been substantially shortened and streamlined to improve clarity and focus. Lines 17-35 Background. The COVID-19 pandemic disrupted healthcare systems, disproportionately affecting individuals with rare diseases. This study explores the health-related quality of life and financial burden in the post-pandemic context among children with Duchenne Muscular Dystrophy and their families in Greece, providing insights into health system performance. Methods. A multicenter, cross-sectional study was conducted in two neuromuscular clinics in Greece. Fifty families (response rate 67%) completed standardized quality of life instruments (PedsQL™ 4.0 Generic Core Scale; PedsQL™ 3.0 DMD Module) and a socioeconomic questionnaire. Descriptive and correlation analyses assessed associations between functional status, financial strain, and psychosocial indicators. Results. Children with Duchenne Muscular Dystrophy reported moderate-to-severe reductions in physical and emotional well-being, and substantial out-of-pocket expenditures. Families with greater financial strain or wheelchair-dependent children had significantly lower health-related quality of life scores. Insurance coverage was positively associated with emotional and psychosocial functioning. Conclusions. Greek families living with DMD continue to face significant financial and psychosocial challenges in the post-pandemic period. While the cross-sectional design does not allow causal attribute to COVID-19 pandemic, the results underscore the need to strengthen financial protection, coordinated multidisciplinary care, and equitable access to support services for rare disease management.

Comment 2: Introduction. The introduction provides a comprehensive overview of DMD and related health policy issues but lacks focus. It should end with a clear rationale, research questions, and objectives tailored to the Greek health system. Several paragraphs discuss global frameworks in excessive detail; these could be summarized to improve flow.

Response 2: We thank the reviewer for this valuable feedback. The Introduction has been substantially revised to enhance focus and clarity. Excessive detail on global frameworks was condensed, and the revised version now concludes with a clear rationale, research gap, and explicitly stated objectives relevant to the Greek healthcare system. This restructuring improves the logical flow and strengthens the contextual relevance of the study. The relevant revised text is in lines 48-70:

Assessing the health-related quality of life (HRQoL) and financial burden associated with DMD has become increasingly important in rare disease research and policy. While global Organizations such as those of the World Health Organization [17] and the European Commission [18] advocate for patient-centered, equity-oriented approaches, studies on DMD often emphasize clinical or cost-related aspects without adequately linking these to the lived experiences of patients and caregivers. Furthermore, international cost-of-illness studies [19-29] conducted in countries such as Spain, Portugal, Italy, Denmark and Japan have demonstrated substantial economic strain but were largely undertaken before the COVID-19 pandemic and rarely integrated validated, disease-specific HRQoL instruments [30-32]. In Greece, research on DMD remains scarce. The country’s health system, characterized by fragmented reimbursement mechanisms and limited financial protection for families affected by rare diseases, faces additional pressures in the post-pandemic era. The pandemic has exacerbated pre-existing gaps in service continuity, rehabilitation access, and social support highlighting the urgent need to examine how clinical severity, caregiving demands, and financial strain interact to influence family well-being. Our study addresses these gaps by providing the assessment of HRQoL using validated Greek versions of the PedsQL™ 4.0 Generic Core and PedsQL™ 3.0 DMD Module instruments [33,34] and socioeconomic burden among children with DMD in Greece’s post-pandemic health system. By focusing on the intersection of socioeconomic, clinical, and psychosocial dimensions, this study provides evidence to inform equitable rare disease management and health policy planning in Greece and comparable healthcare settings.

Comment 3: Methods. The design and use of validated instruments (e.g., HRQoL questionnaires) are appropriate. However, more transparency is needed regarding:

• Sampling (number and location of centers, recruitment procedures).
• Representativeness and justification of the sample size.
• Handling of missing data or incomplete responses.
• Whether ethical approval and informed consent were obtained (as required by Healthcareethics policy).
• The statistical approach, based mainly on descriptive and bivariate analyses, is adequate for an exploratory study, but its limitations should be explicitly acknowledged.

Response 3: Thank you for your comments regarding the Methods section. Relevant to bullets one and two the following revised text is cited in lines 76-88: “.At the design stage, an informal nationwide patient registry (MDA-Hellas) was con-sulted to identify eligible participants, yielding 125 boys aged 5–18 years with a genet-ically confirmed diagnosis of DMD. Within Greece’s four specialized neuromuscular cen-ters, two—AHEPA University Hospital (Thessaloniki) and the University General Hospi-tal of Patras—consented to participate, as they manage the largest patient populations. In total, 75 patients were invited to join the study, representing 60% of all registered cases. Families were approached during routine medical visits to minimize travel burden. Of the 75 families contacted, 50 agreed to participate (response rate: 67%). The main reasons for non-participation were lack of interest, unwillingness to travel, and outdated contact in-formation. The final sample represented the majority of registry-listed pediatric DMD pa-tients in Greece, ensuring reasonable national representativeness. No formal sample size calculation was performed, as the study was exploratory and primarily descriptive in nature.

To address the 3^rd bullet we added the following phrases: in lines 98-102 “In cases where questionnaire items were missing, the following protocol was applied: first, the instrument manual [35] was consulted; second, the missing items were managed according to the prescribed guidelines. When more than 50% of items on a given scale were completed, the mean of the completed items was imputed; otherwise, the scale score was treated as missing.”. And in lines 167-170“The management of missing values with regard to the PedsQL measures was based on the pertinent scoring instructions. With regard to the socioeconomic questionnaire, no missing values were encountered, as this research was of an interview-type nature”.

Regarding the 4^th bullet, the text of lines 103-107 “The study was approved by the Institutional Review Boards of the University of Peloponnese (prot.no. 11415/31-5-2023), AHEPA Hospital (prot.no. 239/16-5-2022), and Patras University Hospital (prot.no. 246/31-5-2022). Written informed consent was obtained from parents or legal guardians of all participants, and assent was obtained from children ≥8 years where appropriate.” is addressing the issue in combination with the Informed Consent Statement: “Informed consent was obtained from both parents or legal guardians in accordance with national regulations for pediatric research, unless sole custody/legal guardianship was documented. Assent was obtained from children aged ≥8 years when appropriate.” in lines 356-358.

Concerning the 5^th bullet, the limitations due to cross-sectional design of the study and the descriptive statistics are acknowledged in the new version of the article in the sections of the abstract, the discussion, the statistical analysis and the conclusion.  

Comment 4: Results The results are comprehensive but too detailed and sometimes repetitive. The narrative should emphasize key findings linking financial burden to HRQoL outcomes instead of restating all descriptive figures. Tables are clear but dense—consider consolidating or moving supplementary data to appendices. Figures should be reformatted with higher resolution (≥600 dpi) and concise legends.

Response 4: We thank the reviewer for this constructive comment. The Results section has been substantially condensed to emphasize key relationships between financial burden and HRQoL outcomes rather than restating detailed descriptive data. Redundant narrative passages were removed, and summary statements now highlight only the most policy-relevant findings. See the revised subsections 3.1, 3.2, 3.3 (pages 4-7, lines 177-234) Regarding the resolution of the figures, we tried the most higher possible.

Comment 5: Discussion. The Discussion section demonstrates wide knowledge of the literature but lacks synthesis. It should focus on:

• How the findings contribute to understanding financial and psychosocial challenges in DMD.
• Comparison with prior European or Mediterranean studies.
• The implications for policy and family support programs.
  At present, the section includes repetitive summaries and tangential commentary that obscure the central argument.

Response 5: We thank the reviewer for their insightful feedback. The Discussion section has been thoroughly revised to enhance synthesis and focus (pages 10-11 lines 258-325)

Comment 6: Conclusions. The conclusions are relevant but still too general. The authors should link them directly to the data and clearly state limitations, including the small sample, regional scope, and cross-sectional design.

Response 6: We thank the reviewer for this helpful comment. The Conclusions section has been revised to link more explicitly to the study’s empirical findings and to include a concise statement of key limitations. The Conclusions section was rewritten accordingly (page 11, lines 327-346).

Comment 7: Language and Style. The manuscript requires moderate to major English editing. Grammar, syntax, and article use are inconsistent. Phrases such as “this investigation have two main research questions” or “to build effective education campaigns” need correction. Sentences should be shortened and written in formal, academic tone.

Response 7: We thank the reviewer for the comment. The entire manuscript has been carefully reviewed for grammar, syntax, and consistency of academic style. Minor edits were made to improve readability and ensure formal tone throughout. Phrases such as those mentioned “this investigation have two main research questions,” “to build effective education campaigns” were not identified in the text. The language now meets the journal’s academic writing standards.

Comment 8: Formatting and References

• Ensure that figures and tables appear in order and are referenced correctly.
• Check that all acronyms are defined at first use (HRQoL, ICC, etc.).
• Verify that references conform to MDPI style (numbered citations in brackets, proper capitalization, DOIs included)

Response 8: We thank the reviewer for this helpful comment. Figures, tables, acronyms, and references were reviewed and corrected to fully comply with MDPI formatting and style requirements

Comment 9: Consider adding a short paragraph in the Methods describing the questionnaires’ validation in Greek populations.

Response 9: thank you for your comment but please note that in the current version under the subsection 2.2 Measures in lines 111-116 there is the following text: “The validated Greek versions of the PedsQL™ 4.0 Generic Core Scales [33] and PedsQL™ 3.0 DMD Module [34] were used, both demonstrating good psychometric properties in prior research. In the present sample, internal consistency reliability was also assessed. Cronbach’s α coefficients exceeded 0.70 across all subscales of the PedsQL™ 4.0 GC and 0.80 for the PedsQL™ 3.0 DMD Module, supporting internal consistency.” We consider the precedent text, quite adequate for the description of the questionnaires’ validation in Greek populations. Further description would be out of the scope of this article since clear citation in the original articles has done.   

Comment 10: Clarify whether any socioeconomic differences between urban and rural respondents were observed.

Response 10: We thank the reviewer for this useful suggestion. Urban–rural differences were examined and incorporated into the revised Results section (see page 7 subsection 3.2, lines 206-221 and the new table 3) and into the Discussion section (see page 10, lines 290-294).

Comment 11: Ensure the Funding, Ethics, and Data Availability statements follow MDPI format.

Response 11: We thank the reviewer for this comment. The Funding, Ethics Approval, and Data Availability statements have been reviewed and reformatted to fully comply with the official MDPI guidelines.

Reviewer 2 Report (Previous Reviewer 3)

Comments and Suggestions for Authors

You can find review in attached file

Comments for author File: Comments.pdf

Author Response

Response to Reviewer 2 Comments:

 Comment 1: Section 3.2 presents data on the proportion of families with different incomes and expenses. The proportion is expressed as a percentage. Due to small samples, the percentages reach 50% or more, which creates a false impression of a large proportion of objects with the given characteristics. For example, Line 320: "51.2% (n = 22) received the extra-institutional care allowance of (€846/month)".  I recommend either providing a confidence interval or simply writing 11 out of 22 families.

Response 1: Thank you for this comment. All relevant information expressed in percentages (%) in lines 227-237, 244-257 and in lines 259-268 has been deleted and expressed in the second suggested way by the reviewer.

We thank the reviewer for this valuable comment. In the revised version, the financial results in Section 3.2 have been rewritten to present absolute numbers and rounded proportions (e.g., “about half of the families” or “22 out of 43 respondents”) instead of precise percentages. This approach avoids misleading impressions given the small sample size and improves clarity without altering the underlying data.

Comment 2: Paragraphs 287-303 discuss statistically significant interregional differences. However, the article does not provide these data or their statistical evaluation.

Response 2: We thank the reviewer for the comment. In the revised text, urban–rural differences were examined and incorporated into the Results section (see page 7 subsection 3.2, lines 207-221 and the new Table 3).

 Comment 3: In this article, the relationship between general well-being and disease-specific problems in children with DMD is assessed based on the correlation coefficient (Table 4). Drawing such conclusions solely based on the correlation coefficient is methodologically flawed and potentially misleading. Correlation does not allow for establishing causal relationships or deep interpretations, such as "a strong association caused by the disease and the pandemic." Furthermore, it requires an interpretation of the correlation strength-for example, weak r<0.3, moderate r=0.3-0.5, or strong r>0.5. The study collected data at a single point in time. Correlation in such designs cannot establish temporal order (which came first: psychosocial problems or DMD anxieties?). Το conclude a "relationship caused by disease progression," longitudinal studies (observation over time) or regression analyses with controlled variables are needed. If the author insists on such a relationship, they can cite the context of the entire study-economic and clinical data, parental feedback, etc.

Response 3: We thank the reviewer for this valuable comment. The presence of Table 4 may potentially engender misleading inferences when attempting to derive causal conclusions regarding the relationship that is precipitated by the progression of the disease. The objective of this study is not to establish a cause-and-effect relationship, but rather to examine the intersection of socioeconomic, clinical, and psychosocial dimensions. The purpose of doing so is to provide evidence to inform the equitable management of rare diseases and the planning of health policy. To facilitate reader comprehension, the table has been omitted. Numeration of the rest of the tables has been addressed accordingly.  

Comment 4: I strongly recommend that the data from Lines 227-236 and 258-269 be tabulated. This data is difficult to understand in text.

Response 4: We thank the reviewer for this helpful comment. In the revised text, the data mentioned in the previously mentioned lines have been tabulated in the new Table 2 on page 5.

Reviewer 3 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

Dear Author(s),

I had the pleasure of reviewing your revision of the manuscript ‘Post-Covid impact on Quality of Life and Financial Burden in Duchenne Muscular Dystrophy: insights into Greek Health System performance from a multicenter study’.

I appreciate that the authors have carefully addressed my previous comments and incorporated the suggested revisions. I have no further remarks at this stage and wish the authors every success with their publication.

 

Author Response

Dear Reviewer

Thank you very much for taking the time to review our revised manuscript and for your positive and encouraging comments. We greatly appreciate your feedback and are delighted that our revisions met your expectations.

Round 2

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

The revised version of this paper meets the quality criteria for publication to this journal. 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript examines the post-COVID impact on quality of life (QoL) and financial burden in children with Duchenne Muscular Dystrophy (DMD) and their families in Greece, using a multicenter, cross-sectional design. The topic is timely, relevant to rare disease policy, and benefits from the use of validated instruments (PedsQL™ 4.0 Generic Core Scale and PedsQL™ 3.0 DMD Module). The multicenter approach adds diversity to the sample. However, the manuscript’s contribution is weakened by methodological opacity, overreach in interpretation, and insufficient contextualization of findings in existing literature.

Major Comments

1. Post-COVID Framing and Attribution

   • The title and introduction imply that observed QoL and financial burden are specifically due to post-COVID circumstances, but the cross-sectional design lacks a pre-pandemic comparator or longitudinal follow-up. Without such data, attributing differences to “post-COVID” effects is speculative. Reframe conclusions to emphasize observed status in the post-pandemic context rather than causal impact.

2. Sampling and Representativeness

   • The manuscript does not clearly state the number of clinics approached, total eligible participants, or response rate. Without this information, representativeness cannot be assessed. Include a flow diagram and detailed recruitment data, as per STROBE guidelines.

3. Measurement of Financial Burden

   • The socioeconomic questionnaire is not described in enough detail. There is no evidence of validation, pilot testing, or alignment with established economic burden frameworks. Provide details on questionnaire development, content, and scoring, and justify the choice of cost categories.

4. Psychometric Considerations

   • While the PedsQL instruments are validated internationally, their adaptation to Greek, particularly the DMD module, should be documented. Were validated Greek versions used? If adapted, was reliability checked in this study?

5. Statistical Analysis Transparency

   • Analysis is limited to descriptive and correlation methods; no multivariable modeling was applied to control for confounding factors (e.g., functional status, socioeconomic status, region).

6. Policy Recommendations Overreach

   • The conclusions include strong policy prescriptions, but these should be tempered given the descriptive nature of the study. Data cannot confirm that observed burdens are new or directly COVID-related.

Minor Comments

1. Tables: Include units for financial figures and clarify currency (€, USD, etc.).

2. Terminology: Maintain consistent use of “quality of life” vs. “health-related quality of life.”

3. References: Some citations (e.g., [18], [19]) are missing page numbers or URLs; ensure MDPI style compliance.

4. Abstract: The methods should mention the number of participants and response rate.

5. Ethical statement: Clarify whether consent was obtained from both parents or legal guardians in pediatric cases.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Author(s),

I had the pleasure of reviewing your manuscript ‘Post-Covid impact on Quality of Life and Financial Burden in Duchenne Muscular Dystrophy: insights into Greek Health System performance from a multicenter study’. The study addresses a highly relevant and timely issue. The study contributes to the literature by exploring the combined effects of the COVID-19 pandemic on health-related quality of life and the financial burden of patients with Duchenne Muscular Dystrophy, while also providing valuable evidence on the performance of the Greek healthcare system. The topic is of great importance not only to clinicians and policymakers but also to researchers in health economics and health services research.

Overall, the manuscript is interesting and provides useful insights. However, I would like to make some specific suggestions that may help to improve the clarity and rigour of the paper:

Comment 1. Abbreviations should be removed from the abstract, as they hinder readability and are not appropriate for this section.

Comment 2. In Table 5, the use of the Mann–Whitney and Kruskal–Wallis tests is not correctly indicated. This should be revised to ensure accurate reporting of statistical methods.

Comment 3. The variables listed in the first row of Table 5 are not defined in the methodology. I recommend that the authors clearly specify these variables in the methods section.

Comment 4. More broadly, the methodology section would benefit from a clearer and more detailed explanation of the variables used and how they were measured. Given the large number of variables, readers may otherwise lose focus. Providing concise definitions and clarifying the measurement process will strengthen the transparency and readability of the manuscript.

Comment 5. In the methodology section a note should be made concerning the ethical approval of the study as well as about respondents consent.

 

Good luck!

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

You can find Review in attached file

Comments for author File: Comments.pdf

Author Response

Please see the attachment.

Author Response File: Author Response.pdf