A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD)

Fraser Philp; Richa Kulshrestha; Nicholas Emery; Marco Arkesteijn; Anand Pandyan; Tracey Willis

doi:10.1371/journal.pone.0268990

Peer Review History

Original SubmissionJuly 28, 2021
14 Oct 2021 Decision Letter - Lucinda Shen, Editor PONE-D-21-20857A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD)PLOS ONE Dear Dr. Philp, 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. The manuscript has been evaluated by two reviewers, and their comments are available below. The reviewers feels that the study is overall well reported, however had some recommendations to further improved the manuscript. In particular, the reviewers have requested some further details to be reported in the technical statistical section of the Methodology. 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Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 6. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: No ****** 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 ****** 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: A pilot study was conducted to investigate the effect of an arm cycling exercise program in people affected by Facioscapulohumeral dystrophy (FSHD). Correlations were observed between strength and (a) shoulder function and (b) rate of perceived exertion of final effort against shoulder function. Minor revisions: 1- Line 197: Identify the statistical methods used for estimating the correlations. 2- Cite the statistical software used for the analysis. 3- Lines 246-279. Provide the percentages that correspond to the frequencies. 4- Figure 5: Indicate that R-squared represents the correlation. State the strength of the correlations according to this table: Coefficient (absolute value) Interpretation 0.90 - 1.0 Very Strong 0.70 - 0.89 Strong 0.40 - 0.69 Moderate 0.10 - 0.39 Weak less than 0.10 Negligible correlation Reviewer #2: A well written exploratory, feasibility study in an area with little focused research. This is greatly needed and I hope the research team will expand this work to the trial phase. There are some issues with this paper that need clarifying prior to being suitable for publication. 1) Please include the make of dynamometer and the type of test, e.g. make or break test 2) There needs to be more justification of the kinematic measurement. If the aim of this work was feasibility and increasing engagement in activity, what was the purpose? In the discussion you mention fatigue changing movement and compensation. If this was the purpose of the kinematic analysis, then this needs to be fully explored in the introduction (experience and potential impact of fatigue, fatigability, trick movements) and the methods (what are changes you are measuring and why). 3) What is the rationale for the intermittent programme? Dosage is not established in FSH and other muscle diseases, but I don't see why this is the exercise prescription is favoured over continuous training. Please clarify. 4) One thought I have as someone who works with this group of people is that the lower limbs are less affected in many cases so for increasing aerobic capacity, general activity and fitness, standard bicycle ergometry will allow them to reach higher work loads, more engagement and get a better training effect. I think you need to be clear about what the training goal here is. I see arm pedalling as being an opportunity to increase strength (as you state) but also muscle endurance and perhaps your prescription should reflect this. The goal of the activity needs to be clearer and linked to the underlying presentation. 5) What are the possible mechanisms of your proposed change (if effective)? Are you increasing the capacity of the compensating muscles? ****** 6. 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 Reviewer #2: Yes:** Dr Gita Ramdharry [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. https://doi.org/10.1371/journal.pone.0268990.r001
Revision 1
18 Nov 2021 Author Response Reviewer #1: A pilot study was conducted to investigate the effect of an arm cycling exercise program in people affected by Facioscapulohumeral dystrophy (FSHD). Correlations were observed between strength and (a) shoulder function and (b) rate of perceived exertion of final effort against shoulder function. AR - The authors would like to thank the reviewer for their time and comments regarding our manuscript. We have made the required changes or hopefully provided sufficient context regarding some of the points raised. 1- Line 197: Identify the statistical methods used for estimating the correlations. 1R - The statistical methods used for estimating correlations have been identified in the manuscript as Pearon’s correlations 2- Cite the statistical software used for the analysis. 2R - The statistical software’s used for the analysis have been reported 3- Lines 246-279. Provide the percentages that correspond to the frequencies. 3R - The percentages that correspond to the frequencies. The n=1 in line 279 is to represent that the references study only has a sample size of 1. 4- Figure 5: Indicate that R-squared represents the correlation. State the strength of the correlations according to this table: Coefficient (absolute value) Interpretation 0.90 - 1.0 Very Strong 0.70 - 0.89 Strong 0.40 - 0.69 Moderate 0.10 - 0.39 Weak less than 0.10 Negligible correlation 4R - An annotation indicating that R2 values represent the correlation between factors has been inserted into the manuscript to support figure 5. Thank you for your suggestion, for the coefficients we would trust the reader to take a decision on the strength of the correlations and would request not to put a value-based judgement according to the suggested coefficient value interpretations. We have therefore not stated the strength of the correlations according to the table. Reviewer #2: A well written exploratory, feasibility study in an area with little focused research. This is greatly needed and I hope the research team will expand this work to the trial phase. There are some issues with this paper that need clarifying prior to being suitable for publication. AR - The authors would like to thank the reviewer for their time and comments regarding our manuscript. We were pleased to read your positive comments. We have made the required changes or hopefully provided sufficient context regarding some of the points raised 1) Please include the make of dynamometer and the type of test, e.g. make or break test 1R) - All available information regarding the make of dynamometer CITEC HHD CT3002 and the type of test (break) have been included. 2) There needs to be more justification of the kinematic measurement. If the aim of this work was feasibility and increasing engagement in activity, what was the purpose? In the discussion you mention fatigue changing movement and compensation. If this was the purpose of the kinematic analysis, then this needs to be fully explored in the introduction (experience and potential impact of fatigue, fatigability, trick movements) and the methods (what are changes you are measuring and why). 2R - Further justification regarding the use of kinematic measurement has been included in the Introduction and Materials and Methodology section. Introduction “There is therefore limited evidence available to inform clinical practice and support strategies for improving physical activity and exercise for people affected by FSHD (8). This includes identification of measures e.g. body structure (e.g. movement features) or body systems responses (e.g. cardiovascular) that can be used to identify fatigue leading to adverse exercise responses or monitoring of changes in control during exercise activities. Given the limited functional capacity and secondary complications experienced in people affected by FSHD, there is a need identify alternate methods for increasing and measuring physical activity engagement that may benefit shoulder function and wider health.” Materials and Methods “This was done to explore if any features of fatigue or adverse responses could be identified based on participant movement profile characteristics.” Please also see our final response to the reviewer 3) What is the rationale for the intermittent programme? Dosage is not established in FSH and other muscle diseases, but I don't see why this is the exercise prescription is favoured over continuous training. Please clarify. 3R) The reviewer raises an important point and we have provided further clarification in the manuscript and amended as below “This exercise programme type was selected as it allows for distinct periods of exercise efforts, between which, patients’ responses to exercise could be evaluated i.e. development of delayed or immediate adverse responses to exercise. As there are no guidelines specific to this exercise intervention in patients with FSHD, the intermittent programme type was a pragmatic selection allowing for consideration of patient safety and evaluation of a dose-response relationship to exercise.” 4) One thought I have as someone who works with this group of people is that the lower limbs are less affected in many cases so for increasing aerobic capacity, general activity and fitness, standard bicycle ergometry will allow them to reach higher work loads, more engagement and get a better training effect. I think you need to be clear about what the training goal here is. I see arm pedalling as being an opportunity to increase strength (as you state) but also muscle endurance and perhaps your prescription should reflect this. The goal of the activity needs to be clearer and linked to the underlying presentation. 4R) Again, the reviewer raises an interesting and important point. We would agree with the reviewer here and have included further elaboration in the introduction This is important as a majority of the impairments in patients with FSHD occur in the upper-limb, limiting activities dependant on upper-limb function and participation. And discussion “Alternate exercise programme variables (e.g. intensity, time, body structure (lower versus upper limb)) may be used to achieve specific or concurrent responses to exercise (e.g. endurance, strength, general physical activity) on the basis of first principle arguments or clinical reasoning, which maybe reflective of current clinical practice. However, these need to be considered against the previously discussed points.” We acknowledge the wider points made by the reviewer re consideration of alternative exercise methods / outcome aims but feel this discussion is beyond the scope of our study. Whilst agreeably correct and interesting discussion topic there is limited available evidence and the aim of our study was to provide some pilot data which may contribute to this boy of work. 5) What are the possible mechanisms of your proposed change (if effective)? Are you increasing the capacity of the compensating muscles? 5R) We acknowledge the point made by the reviewer. At this stage we feel it is too early to say and we are currently undertaking/ planning future studies to investigate this further. We hypothesise the primary aim would be to prevent deterioration given the natural history of the condition. Engagement with the exercise intervention may increase the capacity of the existing muscles / synergies and potentially increase the functional capacity through conditioning of the redundant/ compensatory muscles which are used throughout the disease progression. Currently however we don’t have the evidence for this and would prefer not to commit to a position as of yet. Attachments Attachment Submitted filename: Response to reviewers_R1.docx https://doi.org/10.1371/journal.pone.0268990.r002
13 May 2022 Decision Letter - George Vousden, Editor A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD) PONE-D-21-20857R1 Dear Dr. Philp, 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. Please see my comments below for a minor change that should be made prior to the manuscript's publication. Please accept our apologies for any inconvenience caused by this. 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 for payment will follow shortly after the formal acceptance. 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Kind regards, George Vousden Deputy Editor in Chief PLOS ONE Additional Editor Comments (optional): In the previous round of review, Reviewer 1 requested that the caption of Figure 5 should indicate that the R-squared value represents the correlation. However, as the review notes below, R-squared is actually the coefficient of determination. Before your manuscript is sent your production please either A) remove the text "R2 values represent the correlation between factors" from the figure legend or B) indicate that R2 values represent the coefficient of determination. 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) ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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. 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: Pertaining to the graphs, R-squared is actually the coefficient of determination. In fact, it's the square of Pearson's correlation coefficient. Sorry for the confusion. ****** 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 https://doi.org/10.1371/journal.pone.0268990.r003
Formally Accepted
14 Jun 2022 Acceptance Letter - George Vousden, Editor PONE-D-21-20857R1 A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD). Dear Dr. Philp: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. George Vousden Staff Editor PLOS ONE https://doi.org/10.1371/journal.pone.0268990.r004

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