Benefits of Telerehabilitation for Patients With Severe Acquired Brain Injury: Promising Results From a Multicenter Randomized Controlled Trial Using Nonimmersive Virtual Reality

Background In neurorehabilitation, the use of innovative technologies offers many opportunities to monitor and improve the health status of patients with severe acquired brain injury (SABI). Telerehabilitation allows for continuity of service through the entire rehabilitation cycle, including assessment, intervention, consultation, and education, affording early reintegration and positively enhancing the quality of life (QoL). Objective The main purpose of this multicenter randomized controlled trial was to test the effectiveness of advanced training provided using a nonimmersive virtual reality rehabilitation system (ie, the VRRS HomeKit device) in improving functional outcomes in patients with SABI. Methods In total, 40 patients with SABI and their 40 caregivers visiting 2 Italian rehabilitation centers were enrolled in the study protocol and randomized into 2 groups. Of the 40 patients, 20 (50%) underwent the experimental training using the VRRS HomeKit (teleneuro-VRRS group), whereas the other 20 (50%) were administered usual territorial rehabilitative treatments (UTRTs; control group). To investigate motor and neuropsychological functioning, patients with SABI were evaluated before (T0) and at the end of (T1) each training session by a multispecialist team through a complete clinical and psychometric battery: the Barthel Index (BI), the Tinetti Scale (TS), the Modified Ashworth Scale (MAS), the Montreal Cognitive Assessment (MoCa), the Frontal Assessment Battery (FAB), the Beck Depression Inventory II (BDI-II), the Short Form Health Survey 36 (SF-36), and the Psychological General Well-Being Index (PGWBI). In addition, the Caregiver Burden Inventory (CBI) was administered to each caregiver to investigate the emotional burden status. Results The teleneuro-VRRS group achieved a statistically significant improvement in both general and motor outcomes, as well as psychological well-being and QoL, compared to the control group. In particular, the BI (P<.001), FAB (P<.001), and BDI-II (P<.001) were the outcome scales with the best improvement. The burden of caregivers also significantly improved in the teleneuro-VRRS group (CBI; P<.004). Between-group analysis showed statistical differences in the anxiety (effect size [ES]=0.85, P<.02) and self-control (ES=0.40, P<.03) subtests of the PGWBI and in the social role functioning (ES=0.85, P<.02) subtest of the SF-36, confirmed by quite medium and large ESs. Conclusions Our results suggest that the VRRS is a suitable alternative tool or complementary tool or both to improve motor (level of functional independence) and cognitive (frontal/executive abilities) outcomes, reducing behavioral alterations (anxiety and depression symptoms) in patients with SABI, with a beneficial impact also on the caregivers’ burden distress management, mitigating distress and promoting positive aspects of caring. Trial Registration ClinicalTrials.gov NCT03709875; https://classic.clinicaltrials.gov/ct2/show/NCT03709875

Is this a full powered effectiveness trial or a pilot/feasibility trial? * Manuscript tracking number * If this is a JMIR submission, please provide the manuscript tracking number under "other" (The ms tracking number can be found in the submission acknowledgement email, or when you login as author in JMIR. If the paper is already published in JMIR, then the ms tracking number is the four-digit number at the end of the DOI, to be found at the bottom of each published article in JMIR) TITLE AND ABSTRACT 1a) TITLE: Identification as a randomized trial in the title yes Altro: subitem not at all important 1 2 3 4 5 essential 1a) Does your paper address CONSORT item 1a? * I.e does the title contain the phrase "Randomized Controlled Trial"? (if not, explain the reason under "other") 1a-i) Identify the mode of delivery in the title Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if o ine products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms. Does your paper address subitem 1a-i? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study The title is "Do patients with severe acquired brain injury benefit from Telerehabilitation? Promising results from a multicentric randomised controlled trial using non-immersive virtual Reality." and includes the terms required.

1a-ii) Non-web-based components or important co-interventions in title
Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support"). C a n c e l l a s e l e z i o n e Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study " using non-immersive virtual Reality" 1a-iii) Primary condition or target group in the title Mention primary condition or target group in the title, if any (e.g., "for children with Type I Diabetes") Example: A Web-based and Mobile Intervention with Telephone Support for Children with Type I Diabetes: Randomized Controlled Trial C a n c e l l a s e l e z i o n e Does your paper address subitem 1a-iii? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "patients with severe acquired brain injury" subitem not at all important Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Objective: "The main purpose of this multicenter randomised control trial was to test the effect of an advanced training with a non-immersive virtual reality rehabilitation system (i.e., the VRRS-Home-Kit device) in improving functional outcomes in patients affected by SABI".
Methods: "Forty SABI patients and their caregivers attending two Italian rehabilitation Centres, were enrolled in the study protocol and randomised in two groups. Twenty patients received the experimental training using the VRRS-HomeKit (Tele-Neuro VRRS) whereas the other twenty were submitted to usual territorial rehabilitative treatments (UTRT). To investigate motor and neuropsychological functioning, SABI patients were evaluated before (T0) and at the end (T1)of each training by a multispecialist team through a complete clinical and psychometric battery, including: Barthel Index (BI), Tinetti Scale ( The Psychological General Well-Being Index (PGWBI). In addition, the Caregiver Burden Inventory (CBI) was administered to each caregiver, to investigate the emotional burden status". subitem not at all important 1 2 3 4 5 essential 1b-ii) Level of human involvement in the METHODS section of the ABSTRACT Clarify the level of human involvement in the abstract, e.g., use phrases like "fully automated" vs. "therapist/nurse/care provider/physician-assisted" (mention number and expertise of providers involved, if any). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) C a n c e l l a s e l e z i o n e Does your paper address subitem 1b-ii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "by a multispecialist team " Does your paper address subitem 1b-iv?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Forty SABI patients and their caregivers attending two Italian rehabilitation Centres, were enrolled in the study protocol and randomised in two groups. Twenty patients received the experimental training using the VRRS-HomeKit (Tele-Neuro VRRS) whereas the other twenty were submitted to usual territorial rehabilitative treatments (UTRT Does your paper address subitem 2a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study " it has been shown that VR technology could be useful to stimulate the recovery following stroke [26] and traumatic brain injury [27]. The VR training offer the advantage to simulate daily activities according to patients' needs, in order to motivate patients by avoiding boredom and frustration [28][29], although it requires compliance by subjects. Additionally, use of non-immersive VR tools are more advantageous in being cheaper and easier to use than immersive VR systems. " METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "TR may allow for continuity of services and care through the entire rehabilitation cycle including assessment, intervention, consultation and education, affording early reintegration and positively enhancing QoL ".
"The main purpose of this multicentre randomised control trial was to test the effect of an advanced training with the VRRS-Home-Kit device in improving functional outcomes in patients affected by SABI. Moreover, we sought to investigate the effects of TR on the psychological wellbeing of SABI's caregivers. " Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The enrolled patients were randomly assigned to one of 2 groups " Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Inclusion criteria were: (i) diagnosis of SABI (vascular or traumatic aetiology) in the subacute/chronic phase (i.e., at least 6 months after the event); (ii) age range between 18 and 75 years; (iii) presence of a stable internet connection, and iv) a caregiver able to use simple digital devices.
Patients' exclusion criteria were: (i) severe cognitive and behavioural impairments, (ii) cardio-respiratory instability or other medical illness potentially interfering with the treatment, (iii) severe limb spasticity (Ashworth Scale > 3), and (iv) high-risk of spontaneous fracture. "

4a-i) Computer / Internet literacy
Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clari ed. Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study La tua risposta 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. o ine), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email con rmation, phone calls) were used to detect/prevent these. Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study " Each patient received a complete motor and neuropsychological evaluation before and immediately after the rehabilitation treatment (i.e., at T0 and T1, respectively), administered by skilled physiotherapists, psychologists and/or psychiatric therapists of both Centers (IRCCS Neurolesi Center and San Camillo Hospital). The assessors were blind to the patient's treatment. "

4a-iii) Information giving during recruitment
Information given during recruitment. Specify how participants were briefed for recruitment and in the informed consent procedures (e.g., publish the informed consent documentation as appendix, see also item X26), as this information may have an effect on user self-selection, user expectation and may also bias results.
Does your paper address subitem 4a-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 4b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study IRCCS Neurolesi Center and San Camillo Hospital

4b-i) Report if outcomes were (self-)assessed through online questionnaires
Clearly report if outcomes were (self-)assessed through online questionnaires (as common in web-based trials) or otherwise. Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "he assessors were blind to the patient's treatment. Does your paper address subitem 4b-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study La tua risposta

5-i) Mention names, credential, affiliations of the developers, sponsors, and owners
Mention names, credential, a liations of the developers, sponsors, and owners [6] (if authors/evaluators are owners or developer of the software, this needs to be declared in a "Con ict of interest" section or mentioned elsewhere in the manuscript).
C a n c e l l a s e l e z i o n e Does your paper address subitem 5-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-ii) Describe the history/development process
Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results. C a n c e l l a s e l e z i o n e Does your paper address subitem 5-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial. Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b). C a n c e l l a s e l e z i o n e Does your paper address subitem 5-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study subitem not at all important 1 2 3 4 5 essential 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screencapture video, and/or providing owcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scienti c reporting.
Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login.

Does your paper address subitem 5-vi?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of speci c group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In both the groups each treatment (either cognitive or motor, or both as per patients' functional status) lasted about one hour a day, five days/week, for 12 weeks.
In particular, the experimental group received an advanced motor and cognitive training at home with the VRRS-Home Kit device (Tele-Neuro VRRS) with his/her caregiver acting as a co-therapist, whereas the control group was submitted to usual territorial rehabilitative physical treatments (UTRT) and cognitive training at home. Before their discharge, patients and caregivers were instructed on the use of the device and simulated the training section within the hospital setting to find out potential problems and assess the usability [33]. In detail, both patients and caregivers had three meetings with the telemedicine operators to be provided with the basic information for the correct use of the tool. Then, the SABI patients received six "simulation" training sessions (three times per week for two weeks, each session lasting about one hour). The telerehabilitation simulation was carried out using the tele-cockpit station and the same VRRS-Home kit the patients would have used at home. The instruction training session could be scheduled some other times if the caregiver and/or patient felt insecure about the use of the system. " Does your paper address subitem 5-viii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The experimental training was done using the VRRS HomeKit ( fig.1). It is a tablet placed in a carrying case with sensors, such as K-Wand and K-sensors, that allows to perform at home a complete training program, including motor, cognitive and speech therapy modules. During each training session, the patient was supported by the therapist through the teleworkstation (namely the Tele-Cockpit) and his/her caregiver, having the role of co-therapist to assist the neuropsychologist or the physiotherapist. Tele-Cockpit is an innovative technological workstation equipped with a proprietary integrated videoconferencing system for the management of remote and home devices like the VRRS-HomeKit. The system includes tele-training, tele-monitoring, tele-consultation and streaming of diagnostic imaging. Tele-Cockpit allows the therapist to take control of the remote device and simultaneously see what the patient is doing on the HomeKit, fully interacting with him/her in real time.
Tele-Neuro VRRS sessions included the stimulation of specific cognitive domains, such as attention, verbal and visuo-spatial memory and executive function as well as motor function training using the advanced system, VRRS-HomeKit. The exercises were presented with increasing difficulty and implemented according to the response to the treatment (i.e., when 9 out of 10 correct answers were achieved) and the number of errors (number of errors < 1).
Additionally, therapists could also select the duration of each virtual exercises to better personalize both motor and cognitive tasks, according to patients' abilities, attention levels and needs. "

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum.

Does your paper address subitem 5-ix?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the e-intervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21 -generalizability).

Does your paper address subitem 5-x?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In detail, both patients and caregivers had three meetings with the telemedicine operators to be provided with the basic information for the correct use of the tool. Then, the SABI patients received six "simulation" training sessions (three times per week for two weeks, each session lasting about one hour). The telerehabilitation simulation was carried out using the tele-cockpit station and the same VRRS-Home kit the patients would have used at home. The instruction training session could be scheduled some other times if the caregiver and/or patient felt insecure about the use of the system" subitem not at all important 1 2 3 4 5 essential 6b) Any changes to trial outcomes after the trial commenced, with reasons 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Describe whether, how, and when qualitative feedback from participants was obtained (e.g., through emails, feedback forms, interviews, focus groups).

Does your paper address subitem 6a-iii?
Copy and paste relevant sections from manuscript text La tua risposta Does your paper address CONSORT subitem 6b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study We have not reported any changes to trial outcomes.

Does your paper address subitem 7a-i?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 7b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study We did not perform any interim analyses and stopping guidelines.
Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The enrolled patients were randomly assigned to one of 2 groups using a web-based application for block randomization (www.randomization.com). We used the block randomization method (block size = 4) to ensure balance in sample size across groups over time." Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The enrolled patients were randomly assigned to one of 2 groups using a web-based application for block randomization (www.randomization.com). We used the block randomization method (block size = 4) to ensure balance in sample size across groups over time." 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The enrolled patients were randomly assigned to one of 2 groups using a web-based application for block randomization (www.randomization.com). We used the block randomization method (block size = 4) to ensure balance in sample size across groups over time." 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In both the groups each treatment (either cognitive or motor, or both as per patients' functional status) lasted about one hour a day, five days/week, for 12 weeks.
In particular, the experimental group received an advanced motor and cognitive training at home with the VRRS-Home Kit device (Tele-Neuro VRRS) with his/her caregiver acting as a co-therapist, whereas the control group was submitted to usual territorial rehabilitative physical treatments (UTRT) and cognitive training at home. Before their discharge, patients and caregivers were instructed on the use of the device and simulated the training section within the hospital setting to find out potential problems and assess the usability [33]. In detail, both patients and caregivers had three meetings with the telemedicine operators to be provided with the basic information for the correct use of the tool. Then, the SABI patients received six "simulation" training sessions (three times per week for two weeks, each session lasting about one hour). The telerehabilitation simulation was carried out using the tele-cockpit station and the same VRRS-Home kit the patients would have used at home. The instruction training session could be scheduled some other times if the caregiver and/or patient felt insecure about the use of the system." subitem not at all important 1 2 3 4 5 essential 11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering cointerventions (if any). C a n c e l l a s e l e z i o n e Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study The assessors were blind to the patient's treatment.

11b) If relevant, description of the similarity of interventions
(this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" Informed consent procedures (4a-ii) can create biases and certain expectations -discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator".

Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "the experimental group received an advanced motor and cognitive training at home with the VRRS-Home Kit device (Tele-Neuro VRRS) with his/her caregiver acting as a co-therapist, whereas the control group was submitted to usual territorial rehabilitative physical treatments (UTRT) and cognitive training at home." https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&pli=1&hl=en… 50/76 Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Continuous variables were expressed as mean ± standard deviation (i.e., age and time since injury) or first-third quartile (i.e., psychometric and outcome measures), as appropriate. Categorical variables were expressed as frequencies and percentages (i.e., education and aetiology). Normal distribution of the sample was investigated through the Shapiro-Wilk test, whereas the Levene test to assess the equality of variances among times for each variable. According to reduced sample dimension and not-normality of all variables, we choose a nonparametric-analysis. Thus, where appropriate, outcome measures and psychometric variables were analysed using the one-or two-tailed Wilcoxon signed-rank test was used to detect changes between pre (T0) and post-treatment (T1) within the same group (intra-group analysis); instead, the comparison of continuous variables and outcome measures, between the two groups (inter-group analysis), both at T0 and T1, was performed considering the mean of the Mann-Whitney U test. Linear correlation between variables was calculated with the nonparametric Spearman's rank correlation coefficient. In addition, we calculated the effect sizes (ES) for each psychometric and outcome measures through Cohen's d test between-two groups to describe whether achieved treatment effects have a sufficient magnitude. Statistical significance was set at bilateral alpha level of 0.05. Each analysis was performed on open-source software R 4.1.3 for Windows [43].
In this study, we did not perform an intention-to-treat analysis because heterogeneity might be introduced if non-compliants, dropouts and compliant subjects were mixed together in the final analysis, with potential concerns also on the real/potential efficacy of the treatment. " subitem not at all important 1 2 3 4 5 essential 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses 12a-i) Imputation techniques to deal with attrition / missing values Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).
C a n c e l l a s e l e z i o n e Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In this study, we did not perform an intention-to-treat analysis because heterogeneity might be introduced if non-compliants, dropouts and compliant subjects were mixed together in the final analysis, with potential concerns also on the real/potential efficacy of the treatment."

X26) REB/IRB Approval and Ethical Considerations [recommended as subheading under "Methods"] (not a CONSORT item)
subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "According to reduced sample dimension and not-normality of all variables, we choose a nonparametric-analysis. Thus, where appropriate, outcome measures and psychometric variables were analysed using the one-or two-tailed Wilcoxon signed-rank test was used to detect changes between pre (T0) and post-treatment (T1) within the same group (intragroup analysis); instead, the comparison of continuous variables and outcome measures, between the two groups (inter-group analysis), both at T0 and T1, was performed considering the mean of the Mann-Whitney U test." Does your paper address subitem X26-i?

X26-i) Comment on ethics committee approval
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The study was conducted according to the ethical policies and procedures approved by the local ethics committee (IRCCS-ME 08/2018), and it is part of the registered RCT (NCT03709875) on clinicaltrial.com. All patients' legal guardians gave their written informed consent to study participation and data publication."

x26-ii) Outline informed consent procedures
Outline informed consent procedures e.g., if consent was obtained o ine or online (how? Checkbox, etc.?), and what information was provided (see 4a-ii). See [6] for some items to be included in informed consent documents.

Does your paper address subitem X26-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

RESULTS
13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center

X26-iii) Safety and security procedures
Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline)

Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study 13b) For each group, losses and exclusions after randomisation, together with reasons Does your paper address CONSORT subitem 13a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "All study subjects completed the training, and no adverse event was reported. We found no significant differences between the two groups (including patients and caregivers) concerning age, gender and education. At baseline (T0), our analysis showed no significant differences between the outcome scores of the two groups".
Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT flow diagram) * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study We did not recorded any losses and/or exclusion after randomisation. Does your paper address CONSORT subitem 14a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In both the groups each treatment (either cognitive or motor, or both as per patients' functional status) lasted about one hour a day, five days/week, for 12 weeks. " "The main limitation of the study is the relatively small sample size that prevents us from generalising our promising results to the entire SABI population, in addition to the lack of a follow-up." 14a-i) Indicate if critical "secular events" fell into the study period Indicate if critical "secular events" fell into the study period, e.g., signi cant changes in Internet resources available or "changes in computer hardware or Internet delivery resources" Does your paper address subitem 14a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study 14b) Why the trial ended or was stopped (early) 15) A Does your paper address CONSORT subitem 14b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study The trial was conducted untile the end, whithout any stops.
Does your paper address CONSORT subitem 15? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study " Does your paper address subitem 15-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study In subitem not at all important 1 2 3 4 5 essential 16-i) Report multiple "denominators" and provide definitions Report multiple "denominators" and provide de nitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at speci c pre-de ned time points of interest (in absolute and relative numbers per group). Always clearly de ne "use" of the intervention. C a n c e l l a s e l e z i o n e Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study 20 subjects gave their consent and were exposed to kinds of treatments that lasted one hour a day, five days/week for 12 weeks. 17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval)

16-ii) Primary analysis should be intent-to-treat
Primary analysis should be intent-to-treat, secondary analyses could include comparing only "users", with the appropriate caveats that this is no longer a randomized sample (see 18-i).

Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study La tua risposta Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Between-group analysis showed statistical differences in Anxiety (p< 0.02, ES= 0.85) and Self Control ( subitem not at all important 1 2 3 4 5 essential 17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended 17a-i) Presentation of process outcomes such as metrics of use and intensity of use In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational de nitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is de ned (e.g., timeout after idle time) [1] (report under item 6a).
Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

18-i) Subgroup analysis of comparing only users
A subgroup analysis of comparing only users is not uncommon in ehealth trials, but if done, it must be stressed that this is a self-selected sample and no longer an unbiased sample from a randomized trial (see 16-iii).

Does your paper address subitem 18-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study La tua risposta Does your paper address CONSORT subitem 19? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "All study subjects completed the training, and no adverse event was reported." 22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use). C a n c e l l a s e l e z i o n e Does your paper address subitem 22-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "This multicentric randomised control trial sought to investigate the efficacy of TR nonimmersive VR system on motor performance and cognitive abilities in patients with SABI, as compared to a control group receiving conventional training (URTR). Our results indicated that both experimental and control groups improved in global functional, cognitive and general health status. However, we found that only the Tele-Neuro VRRS group improved also in motor and executive functions with a significant reduction of anxiety and depression symptoms." Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Considering that TR is a growing and potentially efficacious field, it should be analysed in terms of cost and effectiveness [63]. In fact, this analysis should include the cost of technologies (i.e., VR system) and equipment, internet networks and specific maintenance service. In this venue, the primary savings of TR in neurological patients are related to the absence of in-person therapists' costs and mileage reimbursement [63]. On the other hand, costs of face-to-face rehabilitation consider therapists' service, travel expenses both for therapists (i.e., domiciliary therapy) and for caregivers (i.e., ambulatory care) in terms of money, time spent, and effort utilised [64]. Nevertheless, the combination of both approaches (TR and UTRT) will meet the needs of those patients who cannot travel or with higher economic burden. Future studies must analyse the economic issue, comparing the TR costs and the UTRT in neurological patients, with regards to those affected by SABI. Lastly, future research in the TR filed should also measure the group-bytime interaction effect, analysing the extent to which the difference between groups is different at different occasions, through specific statistical tests like RM ANOVA "

20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error. Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events.
Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The main limitation of the study is the relatively small sample size that prevents us from generalising our promising results to the entire SABI population, in addition to the lack of a follow-up. Nonetheless, it was not so easy to enrol a larger and homogenous sample of SABI, also taking into consideration the organisational problems related to the pandemic. One may concern on that we have included both vascular and traumatic SABI, which are known to have a different recovery pattern and functional outcome. However, the aim of the study was to investigate the feasibility and potential efficacy of TR in this patient population to pave the way for a continuum of care. " 21) Generalisability (external validity, applicability) of the trial findings

21-i) Generalizability to other populations
Generalizability to other populations: In particular, discuss generalizability to a general Internet population, outside of a RCT setting, and general patient population, including applicability of the study results for other organizations Does your paper address subitem 21-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other cointerventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting.

Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study About the CONSORT EHEALTH checklist yes, major changes yes, minor changes no X27-i) State the relation of the study team towards the system being evaluated In addition to the usual declaration of interests ( nancial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention.
Does your paper address subitem X27-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study La tua risposta As a result of using this checklist, did you make changes in your manuscript? *