Tele-rehabilitation in Women With Breast Cancer During COVID-19 Pandemic.

METHOD

1. Study design and location This is a longitudinal study of the randomized clinical trialtype. This study will be developed at the Hope Physiotherapy and Esthetics Clinic,headquartered and located in the city of Juiz de Fora, in the state of Minas Gerais.

2. Participants Thirty individuals will participate in the study with a diagnosis of breastCA, previously confirmed by a specialist physician, who attend physiotherapy care at theHope Physiotherapy and Esthetics clinic in the city of Juiz de Fora-MG, authorized bythe owner (ANNEX I).

To calculate the sample size, an alpha value (probability of error type 1) of 5% wasassumed for the two-tailed hypothesis, beta (probability of error type 2) of 20%, testpower of 80% and a difference between groups of 10% referring to engine performancedata. Thus, at least 30 individuals will be needed (Dodd et al., 2002).

All participants will be informed about the objectives and procedures of the study and,when they agree, will sign the Informed Consent Form (FICF). The study will be submittedto the Research Ethics Committee (CEP). Resolution 466/2012 of the National HealthCouncil of 10/10/1996 which regulates research involving human beings and theDeclaration of Helsinki (1964) will be respected. Data will be electronically stored indatabases with restricted and secure access. All data will be encrypted with removal ofany information that could identify individuals.

3. Procedures Thirty women diagnosed with breast AC will be selected to analyze the effecton motor performance, pain, perceived exertion and HRV in interventions through VR.

Ten sessions will be applied (two sessions per week). Initially, the researcher willtravel to the participant's residence with all the protective equipment necessary forthe delivery of the heart rate capture straps, which will be inside a plastic bagdisinfected with 70% alcohol and also to present the consent form and clarified to theparticipants, as well as the procedures and objectives of the study. After signing theconsent form, the following information will be collected through online forms: age,gender, corresponding phase (such as chemotherapy, initial diagnosis, complications,relapse diagnosis), length of stay, associated diseases, medications in use, education .Then, the questionnaires will be applied to the European Organization for Research andTreatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Brunel MoodScale (BRUMS), BORG scale of perceived exertion, and Analog Affective Faces Scale.

Then, training with virtual reality will be carried out, in which the HRV will becaptured (on days 1, 5 and 7) 10 minutes before performing the tasks in a virtualreality environment (at rest, sitting), for 15 minutes during the tasks in VR (MoveHeroand Genius, according to item 5.4.2. D and E) and for another 10 minutes after (at rest,sitting), to assess the autonomic recovery of physical activity. In the 10 days,interventions in VR will be used (MoveHero and Genius and the Borg scale), the HRV andthe other evaluations will be carried out on days 1, 5 and 10.

3.1. Physical Assessment Questionnaires and Tests A) European Organization for Researchand Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) The generalquestionnaire (EORTC QLQ-C30) includes 30 questions related to five functional scales(physical, functional, emotional, social and cognitive), a global health status scale,three symptom scales (fatigue, pain and nausea/vomiting ) and six additional symptomitems (dyspnea, insomnia, loss of appetite, constipation, diarrhea and financialdifficulties).

The score is obtained according to the type of answer chosen. The options allowed by thequestionnaire are "no" (one point), "little" (two points), "moderately" (three points)or "very" (four points). In the two questions referring to the global health statusscale, the options to choose from range from one (very bad) to seven points (very good).Questionnaire scores range from 0 to 100.

Regarding functional and global health status scales, higher scores are related tobetter quality of life; however, for the symptom scales, higher scores correspond to agreater presence of that symptom and, consequently, a worse quality of life (AppendixI).

B) Affective Analog Scale of Faces (FAS):

This scale assesses the affective magnitude of pain through 9 facial expressions thatrange from the feeling of joy to the feeling of sadness, which makes it possible tomeasure the absence of pain to a higher degree of pain (McGrath, 1996).

Facial expressions are sequentially ordered by the letter interval (AI), in which the ADinterval represents the absence of pain, E represents the neutral point and the FIinterval represents different degrees of pain intensities, with F being the easilyignored pain indication by the presence of family members, favorable environment,measures of comfort, safety and understanding of the professional; G an intensity ofpain that does not interfere with behavior and can be mediated by the child'sexpression; There is an intensity of pain that interferes with behavior and requires theuse of analgesics, and I an intensity in the maximum degree of pain that requiresgreater intervention by the team, observation of physical and psychological aspects, inaddition to appropriate analgesic techniques (Torritesi et al., 1998).

Thus, individuals choose among the 9 faces, ordered in a scale from A to I, the one thatmost indicates the intensity of their pain.

C) Borg's perceived exertion scale:

It is the classification of perceived exertion used to measure the subjective intensityof exertion. It is based on sensations experienced during exercise, such as musclefatigue, increased heart rate, and increased breathing (Andrews et al., 2013). It isoften used as an alternative to heart rate to measure the intensity of physical activity(BORG, 1970). The Borg scale has a linear relationship with oxygen uptake (BORG, 1982),in addition to being a measure to determine exercise intensity, while evaluating theoverall physical and mental effort perceived by the individual on physical activity(BORG, 1998).

D) Brunel Mood Scale (BRUMS):

It measures six identifiable affective states (tension, depression, anger, energy,fatigue and confusion.

use) through a 24-item self-report inventory, with respondents rating a list ofadjectives on a 5-point Likert scale from 0 (none) to 4 (extremely) based on subjectivefeelings. Instructions refer to how participants felt last week, including today's date(Van Wijk; Martin; Hans-Arendse, 2013).

3.2. Virtual Reality Training Participants will carry out the tasks individually intheir homes with the help of a computer on a table and with the online presence of theevaluator responsible for providing instructions and recording the results. Height anddistance adjustments will be made according to the individual's needs.

Before starting the task, the researcher will explain the task verbally and a video willbe sent with a demonstration of how the game works. Participants will then complete asingle trial to verify that they understand the instructions.

The following virtual games will be used: Reaction Time (3 adaptation attempts and 10attempts for analysis), Coincident Timing (20 repetitions for motor skill acquisitionand performance improvement), Coincident Timing (5 repetitions + 5 repetitions withlevel increase of speed for analysis of retention and transfer - motor learning), 5repetitions for the transfer phase), Fitts (3 attempts in 4 different difficultyindexes), Genius (5 minutes of training with progressive increase in difficultyaccording to the number of correct answers of the participant), MoveHero (15 minutes oftraining with music according to the number of spheres selected).

A) Task 1 - Reaction time Reaction time is a task that consists of evaluating the timethe subject spends to match his cognitive and motor response with the stimuli given onthe computer screen.

The TRT_S2012 software, built and validated by Crocetta et al., 2017, will be used in asample of 76 healthy adults. The Software proposes a Simple Total Reaction Time (TRT)test, which consists of the appearance of a yellow square (parameterizable) in thecenter of the monitor at previously defined time intervals (ranging from 1.5 to 6.5 ms)and, when given the stimulus, the participant should react as quickly as possible,pressing the space bar on the computer keyboard.

In this activity, the milliseconds that the subject presents of anticipation or delay ofmovement in response to the stimulus will be recorded. This task will test the speed ofcentral and peripheral information processing and will be used in this study as aninstrument to assess cognitive motor training.

The Software also allows a Mental Fatigue Assessment Test from the TRT (TRT Fatigue). Inthis test, the stimulus consists of the appearance of a yellow bar that started at atime previously defined as the interval between stimuli (IEE), following a shift, fromleft to right. As an indication prior to the appearance of the stimulus, a thin verticalbar in black color, simulating a cursor, was presented until the yellow color filled thestimulus bar. The reaction should be to press the space key at the moment the yellowstimulus bar is perceived. The space key must be held down while the yellow color isshown. When the yellow stimulus is stopped, the space key must be released. Yellowstimulus presentation times were previously defined as stimulus presentation time (TAE).This activity will be used in this study as an instrument to assess cognitive motortraining.

B) Task 2 - Coincident Timing The coincident timing task is defined as theperceptual-motor capacity to execute a motor response in synchrony with the arrival ofan external object, at a certain point (Belisle, 1963). This is an interception taskthat involves synchrony between eye and hand movements, requires a movement start,deceleration and "stop" strategy, in addition to accuracy and precision (Fooken et al.,2016; Ohta, 2016). The execution of this first protocol will be performed with theCoincident Timing task using the touchscreen (touch the computer screen).

To evaluate the virtual task, we chose to use a software developed in partnership withthe Information Systems group of the School of Arts, Sciences and Humanities, EACH-USP(first version used by Monteiro et al., 2014) which proposes the 3D coincident timingtask on the computer. This activity will be used in this study as an instrument toassess cognitive motor training.

In the virtual environment, 10 3D circles are displayed on the computer screen thatlight up (red light) in sequence until reaching the last circle that is considered thetarget. The participant must touch the computer screen exactly at the moment when thelast sphere lights up, so the goal is to match the touch on the screen exactly above thelast lit circle (target circle). The software provides immediate feedback on the task'ssuccess or error through different sounds and colors, previously demonstrated (Monteiroet al., 2014, 2017; Bezerra et al., 2018). If the participant hits the target at thesame time as the stimulus arrives, a green light will turn on around the task - hitfeedback, however if the participant delays or advances the movement, a red light willturn on next to the task - feedback from error. The game shows the sequence and speed oflighting the cubes and records the total time of task execution (time taken to touch thesensor); existing errors between stimulus arrival and task completion.

In the design of the coincident timing study, each participant will perform 20 attemptsof the task with the dominant upper limb at moderate speed, that is, 500ms between thelighting of each circle for the Acquisition phase. After acquisition, participants willwait at rest for 5 minutes and then perform five attempts in the Retention phase. As itis considered a simple task, we chose to use short-term retention (Monteiro et al., 2014and Malheiros et al., 2016). For the Transfer phase, five more attempts will be madewith increased speed, that is, 250ms between the lighting of each circle.

Performance during acquisition, retention and transfer tasks will be evaluatedconsidering the difference between target firing time and sensor touch. For thispurpose, performance measures will be used as those related to achieving the"task-coincidence" goal: Constant Error, which reflects the directional trend of themovement, being of delay or anticipation of the response, and calculated using thearithmetic mean of the differences between performance and goal, considering theirsigns; Absolute Error, which corresponds to the accuracy with which the target of theaction was reached, calculated through the arithmetic mean of the absolute differencesbetween the actual performance in each attempt and the target; and Variable Error thatidentifies the precision of the movement, performing the calculation of each attempt,considering the signs, minus the average of the first five attempts for eachparticipant, then the values are raised to the second power and to the average of eachfive attempts, extract the square root (Santos et al., 2003).

C) Task 4 - Fitts The software that simulates the task is "FittsReciprocalAimingTaskv.1.0 (Horizontal)", in the public domain (http://okazaki.webs.com - available from theinternet on 09/01/2010) (Fernani et al., 2017) and was developed by Victor Hugo AlvesOkazaki who presents the task proposed by Fitts' law in a virtual (computer)environment. This activity will be used in this study as an instrument to assesscognitive motor training.

The task that assesses the speed and precision of movement relationship, based on Fitts'Law, consists of performing manual movements directed at a target (blue bars), in 3difficulty indices (ID) with increasing demands for precision. The movement time isobtained through the division between pre-established seconds for the task (10) and thenumber of touches performed on the target.

Before starting the task, the performer must place one of his hands on the mouse, andthe cursor (viewed on the computer) must be in an intermediate point between the twotargets (sidebars). After the initial position, the performer must use the mouse to movethe cursor and click on the targets, two bars, which are arranged parallel vertically,with dimensions and distance determined according to each iID, alternately and asquickly as possible , after the audible alarm is triggered by the computer to start thetask. After 10 seconds a new audible alarm indicates the end of the task. The totalmovement time will be recorded, obtained by dividing pre-established seconds for thetask (10) and the number of touches (10/number of touches).

The task consists of three attempts in each of the difficulty indices (ID 2, ID4a, ID4band ID6), with each index changing the width and distance of the bars with an increasinglevel of difficulty. ID4 was applied in two ways (ID4a and ID4b): in ID4a the distanceand width of bars are larger, in ID4b the distance between bars and width are smaller,keeping the same ID.

For data analysis, the relationship between speed and accuracy of movement described bythe mathematical equation proposed by Fitts will be considered, where there is alog-linear relationship between movement time and task difficulty, with targets ofvarying sizes and distances requiring different times to reach goals (Boyd et al.,2009).

As the size of the target is reduced, or as the distance becomes greater, the movementspeed decreases so that the movement is accurate. Due to the intrinsic informationbetween the tathe target (D) and the distance between them (L), the log2 equation (2D/L)provides a difficulty index (DI) for the targeting skills where, the higher the ID, themore difficult the task. More difficult tasks will require more movement time (Fitts,1954).

D) Task 5 - Genius Game software created in partnership with the Information Systemsgroup of the School of Arts, Sciences and Humanities, EACH-USP, will be used. Among thedifferent games presented by the software, a game that allows motor and cognitivestimuli was chosen, the game presents a memory task where a sequence of colors isemitted by the computer (task based on the game commercially known as "Genius") so thatthe individual then repeat in order to obtain the correct sequence generated. The levelof difficulty increases with each hit of the subject. The virtual interface providesreporting of reaction time and time between touches of each button.

This activity will be used in this study as an instrument to assess memory performanceas well as a component of cognitive motor training.

E) Task 6 - MoveHero Software developed at the School of Arts, Sciences and Humanitiesof the University of São Paulo will also be used. The game features balls that fall, infour imaginary columns on the computer screen, in the rhythm of a song chosen by theresearcher. The task is not to let the balls fall. However, the balls can only betouched when they reach four circles placed in parallel (at two levels of height), twoto the left and two to the right of the participant (0 0 \o/ 0 0), called targets 1, 2 ,3 and 4 as viewed from left to right.

The game captures the participant's movements through a webcam, not requiring physicalcontact to perform the task, so the participant must move their arms, at a distance ofone and a half meters from the computer screen, or through the touch screen thatrequires contact on the computer screen in the inner space of the drawn circles. Theparticipant must wait for the balls to fall, until they start to overlap one of thetarget circles. Therefore, the game requires the participant to have a strategy ofanticipating movement to reach the balls within these circles.

The game offers hit feedback through a numbering (+1) that appears next to the spherethat is successfully hit inside the target, in addition, the total score is visible inthe upper left corner of the screen, with 10 points for each right.

This activity will be used in this study as a memory performance assessment instrumentas well as a component of cognitive motor training.

3.3. Heart Rate Variability (HRV) The analysis of the HRV will follow the guidelines ofthe Task Force of the European Society of Cardiology and North American Society ofPacing and Electrophysiology (TFESC & NASPE, 1996).

The volunteers will be instructed (online) to put on the collection belt given to them.The strap should be placed on the chest, and the heart rate receiver (Elite HRV app onthe cell phone) will be positioned close to the volunteer. The HRV will be recordedafter the initial assessment at rest for 10 minutes, during training with virtualreality for 10 minutes and for 10 minutes after the activity in VR. For analysis of HRVdata at rest and during tasks, 256 consecutive RR intervals will be used.

HR will be recorded beat by beat throughout the protocol by Elite HRV and the RRintervals recorded by the monitor will be transferred (.txt file) to the Kubios HRV®program (Kubios HRV v.1.1 for Windows, Biomedical Signal Analysis Group, Department ofApplied Physics, University of Kuopio, Finland).

Digital filtering will be performed in moderate mode in the program itself (Kubios HRV®)to eliminate premature ectopic beats and artifacts, and only series with more than 95%of sinus beats will be included in the study (Vanderlei et al., 2008).

The analysis of HRV will be performed using linear methods (time and frequency domains)and through non-linear methods that will be analyzed using the Kubios HRV® software.

A) Linear Methods (Time and Frequency Domain) In the time domain, the RMSSD, pNN50 andSDNN indexes will be used. The RMSSD index is defined as the square root of the meansquare of the differences between adjacent normal RR intervals. (Marães et al., 2003).

Where: RR = R-R intervals; N = number of RR intervals in the selected data series.

The pNN50 index, in turn, is a sensitive and easily interpretable marker ofparasympathetic SNA modulation, defined as the percentage of successive differences inthe R-R interval whose absolute value exceeds 50ms. The SDNN, on the other hand,reflects the participation of both ANS branches and corresponds to the standarddeviation of the mean of all normal RR intervals, expressed in ms (Pumprla et al., 2002;Ribeio and Moraes Filho, 2005; Vanderlei et al., 2009).

For the analysis of HRV in the frequency domain, low frequency spectral components (LF - range from 0.04 to 0.15 Hertz) in absolute units and high frequency (HF - variationrange from 0.15 to 0.4) will be used Hertz), in normalized units, and the ratio betweenthese components (LF/HF), which represents the relative value of each spectral componentin relation to the total power, minus the very low frequency components (VLF). Thealgorithm used for the spectral analysis will be the fast Fourier transform - FFT (256 swindow with 50% overlap).

To obtain the spectral indices, a graph (tachogram) is formed that expresses thevariation of RR intervals as a function of time. The tachogram contains an apparentlyperiodic signal that oscillates in time and is processed by mathematical algorithms suchas the Fast Fourier Transform (FFT). The FFT method is used to obtain an estimate of HRVspectral power during stationary phases of the experiment in order to allow comparisonsbetween study results. It allows the tachogram signal to be recovered even aftertransformation by the FFT, which demonstrates the objectivity of the technique, sinceinformation is not lost during the process. The ease of application of this method andgood graphical presentation are the main reasons for its greater use (Carvalho, 2009;Vanderlei et al., 2009).

B) Nonlinear Methods (Trends Debugged Fluctuations Analysis and Poincaré Graph) For theanalysis of HRV by non-linear methods, the Poincaré graph (components SD1, SD2 andSD1/SD2 ratio), DFA (Trends Debugged Fluctuation Analysis) will be used.

The DFA quantifies the presence or absence of fractal correlation properties of RRintervals and has been validated by time series data. This method calculates the rootmean square fluctuation of the integral and debugs the time series, allowing detectionof the intrinsic self-similarity embedded in the non-stationary time series.

The DFA plot is not strictly linear, but consists of two distinct regions of distinctcurves, separated by a point, suggesting that there is a short-term fractal scaleexponent (α1) during periods of 4-11 beats (or 4 to 13), and a long-term exponent (α2),for longer periods (greater than 11 beats) (Carvalho et al, 2009).

Values of α1 close to 0.5 are associated with white noise (random signal; there is nocorrelation between values), while values close to 1.5 are associated with Browniannoise (strongly correlated behavioral signals). Values close to 1.0 are characteristicof fractal-like processes associated with the dynamic behavior of time series generatedby complex systems, such as the autonomic regulation of sinus rhythm in a healthysubject (Godoy et al., 2007).

The Poincaré Graph, on the other hand, is a quantitative method of analysis, based onchanges in the sympathetic or parasympathetic modulation of heart rate over subsequentintervals, without the need for the data stationarity property. The Poincaré is adiagram where each RR interval is represented as a function of RR (i-T), where i is theinterval and T is a predefined delay used for an RR signal. Visual inspection of thediagram has been widely used in the analysis of HRV, where the Poincaré diagram can beanalyzed quantitatively to calculate the standard deviations of the RR intervaldistances. These standard deviations are called SD1 and SD2. This analysis does notrequire pre-processing or data stability, which makes it especially interesting (Godoyet al., 2007).

For quantitative analysis of the plot, the following indices will be calculated: SD1(standard deviation of instantaneous beat-to-beat variability in the short term), SD2(long-term standard deviation of continuous RR intervals) and the SD1/SD2 ratio(Brunetto et al ., 2005). The qualitative analysis of the plot will be done through theanalysis of the figures formed by its attractor, which were described by Tulppo et al.(1998) in: 1) Figure in which an increase in the dispersion of RR intervals is observedwith an increase in the intervals, characteristic of a normal plot. 2) Figure with smallglobal beat-to-beat dispersion and no long-term increase in RR interval dispersion. 3)Complex or parabolic figure, in which two or more distinct edges are separated from themain body of the plot, with at least three points included at each edge.

4. Data analysis For data analysis descriptive statistics will be performed to characterizethe sample and the results will be presented with mean and standard deviation values.

For inferential analysis of tasks in VR, as dependent variables, for "Coincident Timing"and "MoveHero" the error measures in milliseconds will be considered (Constant errorsthat evaluate the directional trend of the movemento, Absolute that demonstrates theaccuracy of movement and Variable that identifies the precision of the movement), for TRthe time and milliseconds, for Genius the number of sequences performed at the beginningand end of the task time, as well as the time between each touch the spheres.

For Fitts, the analysis will be performed by obtaining the values of b0 (intercept), b1(inclination) and r2 (index of determination) for each participant, considering eachattempt in the three difficulty indices. The MANOVA One-way will be used to compare themeans of the groups in the three variables of interest (b0, b1 and r2). To verifyassociations between performance on the motor scale, age, slope of the straight line(b1), intercept (b0) and movement time dispersion data (r2), Pearson's correlationcoefficient will be used. ANOVA will be performed to explore the effects of thedifficulty index on movement time (TM) and multiple regression analysis to find whichfactors influence the TM.

For the analysis of the HRV indices, the Student t-test or Mann-Whitney test will alsobe used for intergroup analyses.

To analyze the influence of independent variables (age, disease stage, medications,etc.) on the dependent variables, the linear regression test will be performed.

A significance level of 0.05 (5%) will be defined and all intervals constructedthroughout the work will have 95% of statistical confidence.

The statistical program will be SPSS (StatisticalPackage for Social Sciences), version26.0.

5. Dissemination and evaluation VR results regarding motor function, pain and HRV will beanalyzed through descriptive and inferential statistical analysis and disseminated inscientific articles, which will be sent to specific journals in the area with a highimpact factor.

Furthermore, the results will be presented in book chapters and at international conferences. Thus, health and education professionals will have more scientific evidence to guide their activities in patients with AC.

Inclusion Criteria:

• Female patients over 18 years old with a diagnosis of breast AC, who agree toparticipate in the research and present an understanding compatible with the executionof the procedures, will be invited to participate in the study.

Exclusion Criteria:

• Exclusion criteria will be non-acceptance to participate in the research; presence ofneurological diseases (infectious diseases, spinal cord injuries, epilepsy) ororthopedic diseases (orthopedic deformities, muscle strains, sprains, dislocations,fractures and pain conditions) in a period of occurrence; inability to play games onthe computer due to motor limitations (fatigue, deformity or muscle weakness),motivational or difficulty in understanding a simple command; metallic skull implants;use of hearing aids; and use of anticonvulsant drugs or muscle relaxants.

Código do estudo:

NCT05530876

Tipo de estudo:

Intervencional

Data de início:

março / 2020

Data de finalização inicial:

dezembro / 2021

Data de finalização estimada:

dezembro / 2022

Número de participantes:

60

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