PONE-D-20-28464

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

PLOS ONE

Dear Dr. Cho,

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

ACADEMIC EDITOR:

In addition to the reviewers' comments, I have a comment. The populations in the studies you have selected are quite different. Some studies have included elderly people with Parkinson's disease or multiple sclerosis, and others elderly people diagnosed with frailty. These people with impaired mobility and / or strength might have a different starting risk if incontinence (or frequent micturition) is present, or develops than in the cohorts without these disorders. Doesn't this require a separate paragraph in the discussion on how this (confounder?) is handled in the manuscripts? You also mention the term 'prompt voiding', the standard term for this strategy is 'prompted voiding', I think.

Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact.

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We look forward to receiving your revised manuscript.

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Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

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: Partly

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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3. 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: No

Reviewer #2: Yes

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4. 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

Reviewer #2: 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: In this systematic review with meta-analysis, the authors focused on the relationship between urinary incontinence and falls. Although the subject is fascinating, the study is penalized by an incomplete submission (tables 1 to 3 are missing) and the absence of subgroup analysis concerning the type of urinary incontinence (urgency vs. stress). It is therefore possible to improve this manuscript by taking into account these 2 points and those that follow:

General comment: Authors should avoid the term "elderly" or "elder" and prefer "older"

1. Abstract: There is a difference between the abstract and the methods in the dates of literature search (october 2019 in the abstract and april 2020 in the methods)

2. Methods:

a. Why did the authors choose as an eligibility criteria studies with population over 20 years? The introduction is developed around the ageing of the population and the fact that both urinary incontinence and falls are geriatric syndromes. I do know that the definition of older age varies widely among countries but 20 years old is definitely not old…

b. Results of the study selection process should be included in the results and not in the methods

c. Data extraction: there is no information on urinary incontinence, its type or severity.

d. Quality assessment. This section should be renamed as: risk of bias assessment. Unfortunately, there is no validation study of the Newcastle Ottawa tool, and no validation of the cut-off used to assess the risk of bias (what is the reference for this cut-off?) Could the authors discuss the choice of this tool and use a more appropriate one?

e. Why the authors did not register their systematic review and meta-analysis protocol? It is well known that the absence of a published protocol can lead to bias (10.1001/jama.287.21.2831).

f. Regarding the search strategy, there is no full electronic search strategy available as it is stated in the PRISMA checklist. Authors should provide it as a supplementary data.

3. Results:

a. The results section is uncomplete since tables 1 to 3 are missing (problem during the submission process?). It is difficult to judge this work without these tables, and I cannot make much more comments without these tables.

b. It seems that there is a problem with the figure 3 (“omitting” in front of each study name). Did the authors proofread their manuscript?

c. The study by Peeters et al in 2019 was included 4 times in the meta-analysis. Could the authors provide an explanation? Are they sure that it was not conducted in the same population?

4. Discussion:

Since we do not have any tables, it is difficult to understand why the authors did not discuss a critical point. I think that the association between UI and falls is rather known and admitted, but the remaining question is “is there any causality between UI and falls”? As the authors said, UI and falls are probably more related to “frailty” and the significant association that many studies highlight may not exist as such.

o Do we have any prospective data to answer this question?

o Do we have some biological hypothesis to support this? (rather not, the authors started to discuss this point but not enough to my opinion, they forgot to include in there discussion the studies published by Dumoulin et al. on gait and urge to void, by Fritel et al. on urinary incontinence subtypes and mobility impairment, etc. )

o Were the studies adjusted on potential confounders? (neurological pathologies? Comorbidities? Polypharmacy?)

o Was the association different if stress or urgency urinary incontinence were considered?

Reviewer #2: I want to congratulate the authors for the idea and development of this manuscript. The paper adds valuable information about the link of falls and UI in terms of higher level of evidence after this systematic review.

I suggest some comments in order to improve quality and understanding of the manuscript:

1. Figure 4 can be omitted, from my view it does not add important information for the reader

2. Please describe acronyms TE/seTE in figure 2.

3. There is a significative statistical heterogeneity in the studies included. This is reflected in the results section, but it is a limitation of the study and need to be commented in the discussion. Probably this point and the quality of the study designs and the reporting scope of the original articles is the main limitation of this meta-analysis.

4. Some studies have shown association between type of UI (specially UUI) and severity (more number of UUI episodes per week). The authors don’t clarify why they don’t include this subgroup analysis. It would be very interesting to have this information in this kind of systematic review.

5. There is a previous systematic review on LUTS and falls that the authors has not mentioned [Noguchi, N., et al., A systematic review of the association between lower urinary tract symptoms and falls, injuries, and fractures in community-dwelling older men. Aging Male, 2016: p. 1-7.]. In this SR none of the identified studies examined potential causes for these associations; the categorisation of continence or not and degree of accounting for confounding variables was inconsistent across the included studies. This point should be discussed and compared with results with your SR.

6. From the point of view of the reader is not clear the categorization in the definition of falls (≥1, ≥2, ≥2 recurrent falls). It would be very helpful to provide a definition of falls (within which time lapse?, what is the definition of recurrent falls?).

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Reviewer #1: Yes: Rebecca Haddad

Reviewer #2: No

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PONE-D-20-28464R1

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

PLOS ONE

Dear Dr. Cho,

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.

==============================

ACADEMIC EDITOR:

Your manuscript has been greatly improved, but, apart from the reviewers comments, I believe I am still missing the answer and / or the processing of my questions to the authors in my earlier letter. Therefore more or less again, in addition to the question of the reviewer to clarify the choice of age categories, I would also like to add some clarification regarding the studies that included persons with a disorder. This is to make it clearer how generalizable your conclusions can be, or how specific they should be. You may therefore have to check, in any case, whether your conclusion is not too general.

==============================

Please submit your revised manuscript by Apr 25 2021 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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: (No Response)

Reviewer #2: 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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: 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 #1: Yes

Reviewer #2: 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: Thank you to the authors for taking our remarks into account and for modifying the manuscript accordingly, which has been considerably improved. Please find additional comments.

Methods

- It is still not clear why this age (≥40 years) was chosen in a study about an essentially geriatric problem. Authors must explain it. Why did they not choose ≥ 60 years old? I only found 2 studies in the results with a possible mean age under 60 (Giraldo Rodriguez L et al. 2019 [29] and Abbs E et al. 2020 [31]). This remark does not mean that I want the authors to remove these studies, but I really want to know the reason behind this selection criteria.

- Study selection: rather use “exposure” than “intervention”

Results

- In table 1, there are some missing informations:

* population characteristics: sex ratio (Tinetti, Johansson etc.), age (de Rekeneire, Huang, etc.) or both (Kim) are missing for some of the studies. Please fill in the missing informations.

* exposition: there is no information on the definition/type/prevalence of UI. Please fill in the missing informations.

* I would merge the 2 columns “definition of falls” and “no. of participants with falls” so that you can add a “UI” column.

* for adjusted OR, I would add, as a footnote under the table, the variables of adjustment.

* when OR is not available, please give the prevalence in the two groups.

* footnotes: missing explanation of the abbreviations: ALSWH, LASA, NSHD, TILDA, UI, CI

* For the study by Stenhagen et al., were the OR calculated on the 6 years or 3 years data? Please indicate the number of participants according to the OR calculation

- Risk of bias assessment

*Figure 2 risk of bias: The authors forgot to adapt the ROBINS-I template to the ROBINS-E tool. For example, D3 bias in classification of interventions is not applicable to the ROBINS-E tool and should be replace by “Bias in classification of exposures”. Please check every single item to be in accordance with the ROBINS-E tool.

*In the manuscript, I think you should explain a little bit more the risk of bias. At least write the major source of bias (bias due to confounding) and highlight the studies who correctly address confounding factors in the relationship between UI and falls.

- Figures 3 et 4 B

The “favours A/favours B” footnote does not work here since authors assess the effect of an exposure and not an intervention. Please modify to something more adequate to this analysis

Discussion

The authors have made some changes regarding the hypotheses to explain of the association between urge UI and falls. But the authors did not make any hypotheses to explain the association between stress UI and falls. To my opinion it is important, and it is one of the most interesting findings of this meta-analysis. Clinicians will remember that urinary incontinence of any type is a factor associated with falls. But authors must make some hypotheses. Is UI just a marker of poor health? Or is UI a real causal factor? Here authors should discuss a little bit more the studies that correctly address confounding factors, especially the ones that could lead to both UI and falls (for example multimorbidity, polypharmacy, neurological diseases, sarcopenia, etc.).

Reviewer #2: I have reviewed this new version of the manuscript. Reviewer's comments and questions have been fully addressed, and the manuscript has increased significantly its quality and understanding.

I am satisfied with the final result. No more comments to add.

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Reviewer #1: Yes: Rébecca Haddad

Reviewer #2: Yes: Salvador Arlandis

[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". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

PONE-D-20-28464R2

Dear Dr. Cho,

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.

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Kind regards,

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

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