## 2 Materials and Methods
### Study Protocol
#### 2.4.2 Instruments  
The instruments used for gathering insightful results included both objective and subjective tools, in order to ensure a comprehensive understanding of the physiological and psychological results collected from the patients. They will be further described based on their corresponding category. Objective Tools--Demographics, Physicians' Evaluation, Scores, and Other In-Game Data  
Objective tools included the collection of demographic data (age group, gender, residence, education, and occupation) as well as the physicians' evaluation, including a category for the affection (neuromotor, musculoskeletal, other), diagnostics, associated affections, and frequency of performing rehabilitation sessions. Another objective tool is represented by in-game data which are automatically collected by the system. This includes accuracy and number of moles hit in a certain level of difficulty (whack-a-mole), score, sublevel, and position of the last punching bag reached (boxing), accuracy, and number of fruits collected (collecting fruits game). The O2 pulse-oximetry ring collected the pulse and oxygen saturation values during the entire testing session, providing, with the help of the associated ViHealth mobile application, additional information such as charts of the evolution of the heart rate, oxygen saturation or motion over time, average values of the heart rate and oxygen level, duration of the recording, and eventual drops in the saturation, as well as distributions of oxygen levels and heart rate ranges. Subjective Tools--Questionnaires and Mental Assessment  
Subjective tools included various questionnaires filled in by the patients based on their self-assessment. These include initial evaluation questionnaires, final feedback questionnaires, and mental assessment self-report instruments (see Supplementary Materials). **Initial evaluation questionnaires** required users to self-assess various competencies such as the following:  
* Technological experience level:
* Inexperienced (not using technology);
* Little experience (using just their mobile phone with various applications);
* Medium experience (satisfactorily managing several devices and applications, including laptops, smartwatches, and internet browsing);
* Very experienced (efficiently managing various devices and applications, including laptops, smartwatches, and internet browsing). * Experience with virtual reality:
* Inexperienced (not knowing the meaning of it/never tried it);
* Low experience (tested VR at least once);
* Medium experience (used multiple applications in VR);
* Very experienced (used various applications in VR in an efficient way). * Preferred level of difficulty of games--scale from 1 (very easy) to 5 (very difficult). The **final feedback questionnaire** required users to evaluate the following aspects related to the games and their personal experience during the tests:  
* Enjoyment, ease of use, motivation, relaxation for whack-a-mole, boxing/collecting fruits, breathing, progressive muscle relaxation, on a scale from 1 (not at all) to 5 (very much);
* Usefulness for anxiety/panic attack management for breathing and progressive muscle relaxation, on a scale from 1 (not at all) to 5 (very much);
* Comfort of testing the exercises in virtual reality, on a scale from 1 (uncomfortable) to 5 (very comfortable);
* Justifications for any score less than 3 in the previous questions;
* If they would use the proposed system at home, in a telemedicine program (yes/no/do not know);
* Other suggestions for improvement/future development. The clinical **psychological instruments** we have used in this research are standardized and calibrated for the Romanian population and are part of a large kit of psychological assessments largely used in Romania and produced by Romanian Psychological Testing Services Cluj-Napoca since 2007. The **Self-Efficacy Scale** (SES) is a self-assessment instrument that reveals the individual's belief about personal resources involved in managing difficult situations across their lifespan.