Safety, feasibility, acceptability and preliminary effects of the Neurofenix platform for Rehabilitation via HOMe Based gaming exercise for the Upper-limb post Stroke (RHOMBUS): results of a feasibility intervention study

Objectives To investigate the safety, feasibility and acceptability of the Neurofenix platform for home-based rehabilitation of the upper limb (UL). Design A non-randomised intervention design with a parallel process evaluation. Setting Participants’ homes, South-East England. Participants Thirty adults (≥18 years), minimum 12-week poststroke, not receiving UL rehabilitation, scoring 9–25 on the Motricity Index (elbow and shoulder), with sufficient cognitive and communicative abilities to participate. Interventions Participants were trained to use the platform, followed by 1 week of graded game-play exposure and 6-week training, aiming for a minimum 45 min, 5 days/week. Outcomes Safety was determined by assessing pain and poststroke fatigue at 8 and 12 weeks, and adverse events (AEs). Impairment, activity and participation outcomes were measured. Intervention feasibility was determined by the amount of specialist training and support required to complete the intervention, time and days spent training, and number of UL movements performed. Acceptability was assessed by a satisfaction questionnaire and semistructured interviews. Results Participants (14 women; mean (SD) age 60.0 (11.3) years) were a median of 4.9 years poststroke (minimum-maximum: 1–28 years). Twenty-seven participants completed the intervention. The odds of having shoulder pain were lower at 8 weeks (OR 0.45, 95% CI 0.24 to 0.83, p=0.010) and 12 weeks (OR 0.46, 95% CI 0.25 to 0.86, p=0.014) compared with baseline. Fugl-Meyer upper extremity, Motor Activity Log and passive range of movement improved. No other gains were recorded. Poststroke fatigue did not change. Thirty mild and short-term AEs and one serious (unrelated) AE were reported by 19 participants. Participants trained with the platform for a median of 17.4 hours over 7 weeks (minimum-maximum: 0.3–46.9 hours), equating to a median of 149 min per week. The median satisfaction score was 36 out of 40. Conclusion The Neurofenix platform is a safe, feasible and well accepted way to support UL training for people at least three months poststroke. Trial registration number ISRCTN60291412.


GENERAL COMMENTS
In the abstract conclusion (page 4, line 5) and in the conclusion (page 23, line 29) I think using the term "acceptable" is misleading, as acceptable would rather indicate its viability as a rehabilitation procedure, which is linked to its effect more than to its acceptance. "well-accepted" could be a suitable replacement.
In the sample size section, authors state "We estimated 30 individuals would be sufficient". How was this estimated?
Concerning AEs, why do authors claim there were 11 unrelated AEs? What is the specific criteria to determine a certain AE as related or unrelated?
Finally, and although not related to the study design itself, I am interested in the lack of adherence. Authors state that, ideally, patients should perform their rehabilitation for approximately 45 minutes per day and 5 times per week. I understand about 25% of participants did exercise this much. Is there any available information on what is the adherence to a comparable therapy plan (that is, 225 minutes per week) using different (e.g. non-gamified) approaches? Given that the theoretical advantage of gamified therapy is that it should be more appealing and thus increase adherence, this is worrying. This should also perhaps be described in the discussion in more detail, comparing it with related approaches and potential solutions.

REVIEWER
Dorsch, Simone South Western Sydney Local Health District, Bankstown-Lidcombe Hospital REVIEW RETURNED 23-Jun-2021

GENERAL COMMENTS
This is a very clearly written manuscript and I commend the authors for their clear language and easy layout of information. I have minor suggestions only. Abstract Results do not contain the UL impairment/ activity outcomes -it would be good to read these in the abstract Methods Outcomes -it would be good to explain what is meant by 'a utility value using the cross-walk function' as this is not as familiar as other outcome measures Safety -in this description, it is not clear if pain and fatigue are adverse events. If fatigue is being called an adverse event it would be good to understand if the intervention was related to increased fatigue and the severity of the fatigue. It is also arguable as to whether fatigue in the context of exercise is an adverse event, as exercise that does not induce some fatigue is probably not intensive enough to be of benefit.

VERSION 1 -AUTHOR RESPONSE
Reviewer: 1 1. In the abstract conclusion (page 4, line 5) and in the conclusion (page 23, line 29) I think using the term "acceptable" is misleading, as acceptable would rather indicate its viability as a rehabilitation procedure, which is linked to its effect more than to its acceptance. "well-accepted" could be a suitable replacement.
Thank you for this suggestion, we have adjusted the term 'acceptable' to 'well-accepted' throughout the manuscript 2. In the sample size section, authors state "We estimated 30 individuals would be sufficient". How was this estimated?
We acknowledge the use of the word 'estimated' is misleading and have re-written the sentence as follows: We included 30 participants based on recommendations that between 24 and 50 participants are sufficient for feasibility studies. [32,33] 3. Concerning AEs, why do authors claim there were 11 unrelated AEs? What is the specific criteria to determine a certain AE as related or unrelated? This should also perhaps be described in the discussion in more detail, comparing it with related approaches and potential solutions.

Reviewer: 2
This is a very clearly written manuscript and I commend the authors for their clear language and easy layout of information. I have minor suggestions only.
Thank you for your kind comment on the paper.

Abstract:
Results do not contain the UL impairment/ activity outcomes -it would be good to read these in the abstract 7. Safety -in this description, it is not clear if pain and fatigue are adverse events. If fatigue is being called an adverse event it would be good to understand if the intervention was related to increased fatigue and the severity of the fatigue. It is also arguable as to whether fatigue in the context of exercise is an adverse event, as exercise that does not induce some fatigue is probably not intensive enough to be of benefit.
Thank you for highlighting these areas for clarification. We have specified that fatigue is post-stroke fatigue and have adjusted the wording throughout to make this clearer.