Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article needs to be significantly improved.

1. Unfortunately, what stands out from the beginning is the gluing of different sentences together. It doesn't look good and doesn't read well.

2. The authors wrote a review article, the methodology suggests that it was supposed to be a systematic review, but it's not known. Inclusion and exclusion criteria were introduced, but what came out of it is missing. How many articles were taken into account, how many were ultimately reviewed, how many of them were cited? I suggest adding a flow diagram in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

3. The tables are missing the doses of substances used and the number of daily applications.

4. The table for Traditional Medicinal herbs ishould be added.

Comments on the Quality of English Language

English should be corrected by Native.

Author Response

 

Dear Reviewer,

 

Thank you for your feedback on our manuscript. We have considered your comments and made the necessary revisions to improve the clarity, structure, and content of the paper. Below are our responses to your specific points:

 

1. Writing Style and Sentence Structure: We have revised the manuscript to improve the flow and readability of the text.

 

2. Methodology and PRISMA Flow Diagram: We have refined the description of the methodology, and we have included a PRISMA-style flow diagram to provide a clear overview of the selection process, showing how many articles were initially identified, screened, and included in the review.

 

 

3. Doses and Frequency of Application in Tables: We have updated the tables to include these details where available, providing a more comprehensive summary of each study's protocols and interventions.

 

4. Addition of a Table for Traditional Medicinal Herbs: Based on your recommendation, we have integrated the medicinal herbs into Table 3 nd organised innovative treatments into a separate fourth table. These updates now offer an overview of both traditional and innovative treatments, detailing proposed effects, dosages, and application methods where available.

 

 

The manuscript has been thoroughly reviewed and edited  to ensure clarity, grammatical accuracy, and appropriate use of  English language.

Reviewer 2 Report

Comments and Suggestions for Authors

This review discusses the dry mouth, a common condition caused by factors like medication and radiation therapy, remains challenging to treat effectively. While topical treatments like saliva substitutes and stimulants offer some relief, their efficacy varies and they often require frequent application. Traditional medicine, including herbal remedies, shows promise but requires further validation. Emerging therapies like electrostimulation, photobiomodulation, and hyperbaric therapy show potential but require more clinical evidence. Therefore, the search for effective and sustainable dry mouth management strategies continues. This manuscript can be accepted if solving the following comments.

1.      How do different types of saliva substitutes compare in terms of their effectiveness, ease of use, and patient compliance?

2.      Are there any adverse effects associated with the use of saliva substitutes or stimulants that are not mentioned in the review?

3.      Studies on other emerging therapies such as stem cell therapy, gene therapy should be included in this review.

4.      How about the roles of potential benefits of lifestyle changes, such as increased water intake and avoiding known triggers of dry mouth? What is the role of water intake in dry mouth management?

5.      A big missing of this review is the role of lubrication. Various aqueous dispersions of macromolecules have been proposed to assist or replace the saliva in these patients. It is vital that these macromolecules have ample lubricity and water retention properties while showing long-lasting efficacy, according to the review published on Lubricants (Lubricants 2024, 12, 126. https:// doi.org/10.3390/lubricants12040126). Therefore, the reviewer strongly suggests the authors to describe the role of lubrication in dry mouth treatment, especially these literatures (J Texture Stud. 2021; 52: 141–156. https://doi.org/10.1111/jtxs.12575; Friction 10(8): 1137–1165 (2022), https://doi.org/10.1007/s40544-021-0586-1; Prog. Polym. Sci. 2020, 110, 101298, https://doi.org/10.1016/j.progpolymsci.2020.101298; Archives of Oral Biology, 2012, 57(8), 1121-1126, https://doi.org/10.1016/j.archoralbio.2012.05.007; Langmuir 2018, 34, 11281−11291, DOI: 10.1021/acs.langmuir.8b01722) should be cited and discussed further.

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

Thank you for your comments and insightful observations on our manuscript. Below we provide detailed responses to the points you raised, along with the necessary revisions to enhance the clarity of our review.

1. It is really difficult to compare the studies evaluating the ability of the substitutes. This is because the great difference in materials and methods, including a wide range of formulations of the same substitute, different number of somministrations, dissimilar time point assessments, different inclusion/exlusion criteria of the patients and to diagnostic xerostomia.

 

2. Conversely by the sistemic drugs, no important adverse effect has merged using the substitutes and stimulants at the reported doses.

 

3. We have expanded the manuscript to include emerging therapies, such as stem cell therapy, and gene Additionally, we have incorporated more studies on acupuncture.

 

4. We have elaborated on the role of lifestyle modifications, particularly increased water intake and avoidance of xerogenic triggers (e.g., alcohol, caffeine, tobacco). These strategies are highlighted as adjunctive measures to improve symptoms of xerostomia by supporting hydration and reducing environmental or behavioural contributors.

 

5. Further, we particularly thanks the reviewer to invite us to talk more about lubrification, cureful reading the indicated papers and then focusing on the role of lubricants in providing sustained relief and support to oral health cure in xerostomia. We also included the references in our bibliography.

 

 

 

 

 

Reviewer 3 Report

Comments and Suggestions for Authors

Review of the Manuscript: "Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies"

The manuscript addresses an important clinical issue, but it requires significant reorganization and clarification before being suitable for publication.

General Comments:

Even if the authors did not mention in the title, the review is resembling more as a narrative review.

Although this is not a systematic review, the authors should include a detailed search strategy. Providing information on the databases used, key search terms, inclusion criteria, and time frame for the reviewed studies will lend more credibility to the narrative and ensure that the review is comprehensive and up-to-date. I recommend following the guidelines outlined in Baethge et al. (2019)[ (Baethge, C., Goldbeck-Wood, S. & Mertens, S. SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev 4, 5 (2019). https://doi.org/10.1186/s41073-019-0064-8 )], which suggest that even narrative reviews need a transparent and structured methodology.

There are many flaws to be addressed before being suitable for publication. Some are as follows:

The search strategy needs to be transparent and reproducible, with full details provided in the Materials and Methods section.

The inclusion of studies needs to match the aim, or the aim should be revised to reflect the actual scope of the review.

Grouping the therapeutic approaches by the underlying etiology of xerostomia will provide better structure and clarity.

Tables should be revised to include essential study details, and the discussion should be expanded with appropriate references. Furthermore, the search strategy needs to be transparent and reproducible, with full details provided in the Materials and Methods section.

Implementing these suggestions will significantly enhance the manuscript's quality and usefulness for clinicians and researchers alike.

Here are the detailed comments

Abstract

The abstract needs to follow a structured format, including the following sections: Background, Aims, Materials and Methods, Results, and Conclusion. This will improve clarity and allow readers to quickly understand the study's key elements.

Introduction

The novelty of the study needs to be clearly highlighted in the introduction, along with a more precise statement of the aim. The current aim of the study is to "summarize the knowledge in treating xerostomia." However, the inclusion criteria are primarily focused on xerostomia caused by malignant tumoral (cancer) etiology, which does not align with the broader aim. Since xerostomia can result from various causes such as drug-induced, autoimmune-related (e.g., Sjögren’s syndrome), and other conditions, this lack of clarity creates confusion. If the intention is to review xerostomia treatments comprehensively, the inclusion criteria should be expanded to include all causes. If the focus is solely on cancer-related xerostomia, the aim should be revised accordingly. This discrepancy needs to be addressed to avoid further confusion.

Materials and Methods

The manuscript lacks sufficient detail about the search strategy, which is crucial for transparency and reproducibility. Here are some points that need to be clarified:

• Databases searched: Please specify the databases used, such as PubMed, EMBASE, Web of Science, Google Scholar, etc.
• Search period: Define the search period clearly, especially what is meant by "the last 10 years" as mentioned in the abstract. Exact dates or a clear time frame should be provided.
• Handling duplicates: Clarify the process used for removing duplicates—whether this was done manually or using software—and specify how many articles were excluded due to duplication.
• Flow of article selection: Even though this is not a systematic review, including a PRISMA flowchart would help visualize the process, showing the number of studies retrieved, duplicates removed, and the final number of articles included in the review.

Organizational Structure

The manuscript lacks a clear and logical organizational structure, making it difficult to follow. To improve readability, I suggest grouping therapeutic approaches based on the underlying etiology of xerostomia. For instance, treatments for radiation-induced xerostomia should be discussed separately from treatments for drug-induced or autoimmune-related xerostomia. This would provide a clearer understanding of cause-effect relationships and allow readers to better comprehend which treatments are suitable for each type of xerostomia.

Tables

Both Table 1 and Table 2 lack important details. It is recommended to include:

• The first author of each study.
• The number of patients enrolled in each study.
• Whether the studies are Randomized Controlled Trials (RCTs) or another study design.

These details are crucial for evaluating the quality of the evidence. Without this information, readers cannot properly assess the strength and reliability of the findings presented.

Results

In the "Topical Therapy" section, it would be beneficial to group salivary substitutes based on the underlying cause of xerostomia. For example, salivary substitutes for radiation-induced xerostomia should be discussed separately from substitutes used for drug-induced xerostomia. This approach should be applied across the entire manuscript for all therapeutic options, ensuring that each treatment is aligned with a specific etiology. Additionally, instead of the detailed explanations in this section, I suggest moving the detailed methods to the Discussions section and focusing on reporting the results of the search and the number of included studies in this section.

Discussions

The Discussion section lacks sufficient references to support the claims made. The authors should include more citations to back up their interpretations and compare their findings with existing literature. Doing so will provide stronger scientific grounding and improve the manuscript’s academic rigor. Additionally, the Discussion should critically analyze the reviewed studies and the methods used, offering insights into any conflicting results or limitations.

Conclusions

The conclusions need to be more specific, reflecting the key findings and summarizing the most effective methods for treating xerostomia based on its etiology. The conclusions should directly relate to the therapeutic approaches discussed in the manuscript and offer clear takeaways for clinical practice.

Comments on the Quality of English Language

The English language throughout the manuscript needs improvement for clarity.

Beside this, there are mistaken words or expressions. Some examples are “funtions” – row 527 or the entire sentence with duplicate words “In such a way, the molecules are capable to provide multi-target benefits to restore the homeostatic systems in cells and tissues, where an impairment of metabolism or protein/peptide dysregulation has occurred an impairment of metabolism or protein/peptide dysregulation has occurred” (rows 580-582).

Author Response

Dear Reviewer,

 

Thank you for your  constructive comments. We have  reviewed your suggestions and made revisions to improve the structure, clarity, and quality of the manuscript.

 

Below are our responses to your specific points:

 

Abstract

We have restructured the abstract to include the following sections: Background, Aim, Materials and Methods, Results, and Conclusion.

 

 

Introduction

We have revised the introduction to better highlight the novelty of our study and to clarify the study’s aim. Additionally, we have adjusted the inclusion criteria to align more closely with the broader aim of reviewing treatments for xerostomia from various causes, not limited to cancer-related xerostomia. This should address the inconsistency between the aim and the inclusion criteria that you pointed out.

 

Materials and Methods

We have clarified in the Materials and Methods section that PubMed, EMBASE, and Web of Science were used as primary databases, the search period covers studies from January 2013 to January 30, 2023, duplicates were removed manually with the number indicated, and a PRISMA-style flowchart has been added to illustrate the selection process, including retrieved studies, duplicates removed, and final articles included.

 

Tables

We have revised Tables 1 and 2 to include the first author of each study, the number of patients enrolled, and the study design (e.g., RCTs or other designs), providing more context to evaluate the quality and reliability of the evidence presented. Additionally, we have added Tables 3 and 4, which group the data to offer a clearer understanding of the therapeutic approaches for managing xerostomia.

 

Results

We have reorganized the Results section by grouping therapeutic approaches according to the underlying etiology (e.g., radiation-induced, drug-induced).

 

Discussion

We have enriched the Discussion section with additional references to support our interpretations and to compare our findings with existing literature. We have also critically analyzed the reviewed studies and their methodologies, addressing any conflicting results or limitations. This provides a stronger scientific foundation for our conclusions.

 

Conclusion

We have made the conclusions more specific and aligned them with the main findings of the manuscript.

 

 

Comments on the Quality of English Language

 We have reviewed and edited the manuscript for clarity and accuracy in English language use. Specific instances of mistaken words or phrases have been corrected.

 

Thank you again.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors significantly corrected the manuscript according to the reviewer's suggestions. Recently, I recommend the article for publication.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have solved my concerns.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors adequately addressed the comments provided in the first round of review. I appreciate their thorough responses and the significant improvements made to the manuscript. I recommend its publication in the current form, with minor language revisions.