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TRANSCRIPT
Running head: RCT OF MITII FOR EF WITH ABI 1
Introduction
Acquired Brain Injury (ABI) is the major cause of death and disability in children and
adolescents and is defined as any insult to the brain in the post-neonatal period resulting from
either traumatic or non-traumatic aetiologies.1 It is burdensome and leads to a plethora of
health outcomes including deficits in cognitive, behavioural, psychological, and physical
functioning.2-4 Cognitive impairments including executive dysfunction are common following
an ABI.2,5-7
Executive function (EF) refers to the skills which are necessary for behaviour to accomplish
goal directed activities.8,9 Anderson’s paediatric model published in 2002 describes EF as a
sum of inter–related and inter-dependent processes which function together as a supervisory
system. The model has four distinct domains of (i) attentional control – which includes the
capacity to selectively attend to specific stimuli; (ii) information processing –the fluency,
efficiency and speed at which information is processed; (iii) cognitive flexibility –the ability
to shift between response sets and learn from mistakes and divide attention; and (iv) goal
setting – which incorporates the ability to develop new initiatives and concepts.5 Deficits in
this area can lead to many functional limitations which can have devastating effects on school
attainment, social development, behavioural regulation, and participation in everyday
activities.2,6,10,11
There is limited evidence for cognitive rehabilitation following an ABI in the paediatric
population.6,12,13 It has been demonstrated that varying levels of efficacy for cognitive
interventions with functions such as memory and attention respond better to targeted
interventions when compared to processing speed.6,12,13 Attention rehabilitation in the
paediatric ABI population has shown some positive effects for attention training and for the
use of compensatory strategies to compensate for attention difficulties following ABI.13 In
terms of the rehabilitation of executive functioning in the paediatric ABI population, there is
RCT OF MITII FOR EF WITH ABI 2
a paucity of evidence with most interventions focusing on a single aspect of EF such as
problem solving rather than multiple components of a system.13 Commensurate with these
findings, only three studies were indentified in a recent systematic review into the use of
technology-based rehabilitation strategies for executive dysfunctions in children and
adolescents with Traumatic Brain Injury (TBI).14 A meta-anlysis of these three studies only
found small to medium effects when evaluating the intervention group immediately post-
treatment compared to the placebo group using a web-based problem solving approach.14
Evidence-based recommendations from the 2007 review of cognitive and behavioural
rehabilitation treatments in children with ABI included a need for experimentally derived
studies with random assigned experimental-control groups.13 They also highlighted the
importance of active family involvement as treatment providers. The implications of the
systematic review conducted in 2016 recognised the significance and potential of internet-
delivered interventions as a way to reduce cost to family, the healthcare burden, and increase
convenience for all stakeholders.14 There is caution however, that as technology advances and
web-based interventions are developed, rigorous testing needs to be undertaken to assess the
benefit to all stakeholders and to determine whether these interventions surpass current
practices or act as adjuncts.14
“Move it to improve it” (Mitii™ ) is a novel, internet-based, multi-modal rehabilitation
program that offers intense and incrementally challenging training in the cognitive, visual
perceptual, and physical (i.e. upper limb and gross motor) function areas. The feasibility of
the program has been demonstrated in a small non-randomised pilot study of children aged 9-
13 years with UCP.15 The premise behind the program is 30 minutes of training, 6 days per
week, over 20 weeks would be sufficient to drive neuroplastic changes in the brain.16 The
second generation Mitii™ program used for the current study utilised Microsoft Kinect
(Microsoft Research, Redmond, Washington, USA) technology to track the body movements
RCT OF MITII FOR EF WITH ABI 3
of children as they completed each training module (Boyd et al., 2015). Virtual trainers
(Physiotherapist, Occupational Therapist, and Neuropsychologist) select from 11 Mitii™
training modules comprising 60% combined cognitive, visual perceptual, and upper limb
activities, and 40% gross motor based activities, and tailor a rehabilitation program unique to
each participant.17 As participants progress through their tailored training program, the virtual
trainers incrementally increase the intensity and complexity of the modules at weekly
intervals. Virtual trainers also provide regular support by weekly phone calls and/or email,
depending on family preference.17
While the Mitii™ program was originally designed for children with UCP (Boyd et al.,
2013), there is potential value of implementing this rehabilitation intervention in children and
adolescents with ABI who also experience cognitive, perceptual, and motor difficulties.
Based on the concepts of neuroplasticity and restorative approaches to rehabilitation, Mitii™
has the potential to improve executive functioning abilities in the paediatric ABI population
through repetition, consistency, and is supported by ease of use, is cost-effective, and relies
on family engagement. The aim of this RCT was to examine the effects of Mitii™ ™ on EF,
specifically attentional control, cognitive flexibility, goal setting, and information processing
in children with ABI. The primary hypothesis was that Mitii™ would improve performance
on tests of EF. A secondary hypothesis was that Mitii™ would improve parent ratings of
everyday EF as measured by a parent questionnaire.
Method
This parallel group randomised controlled trial was conducted according to CONSORT
guidelines in Brisbane between June 2013 and January 2015. Full ethics approval was
obtained from The Royal Children’s Hospital, Brisbane (HREC/12/QRCH/222) and from the
Medical Ethics Committee of The University of Queensland (2013000212). This RCT study
RCT OF MITII FOR EF WITH ABI 4
was registered with the Australian and New Zealand Clinical Trials Registry
(ANZCTR12613000403730).
Participants
The sample consisted of children and adolescents recruited across Queensland and New
South Wales who were at least 12 months post ABI that was acquired ≥28 days after full term
birth. To be included in the study participants had to i) be aged 8-16 years old; ii) be
functioning at an equivalent level of Gross Motor Function Classification Scale (GMFCS)18 I
or II; iii) have Manual Abilities Classification scale (MACS I, II, III, iv)19 have sufficient
cognitive understanding, visual and verbal abilities and co-operation to participate and
perform the required tasks; v) be medically diagnosed with an ABI and be classified with
either mild, moderate or severe complicated brain injury; and vi) be able to access the internet
at home (i.e. phone line or internet access). Children and adolescents were excluded from the
study if they had i) unstable epilepsy (i.e. frequent seizures not controlled by medication); ii)
a degenerative or metabolic condition; or iii) undergone any surgical or medical intervention
in the 6 months prior to starting the study. The GMFCS is a classification system that
assesses children’s abilities to carry out self-initiated movements whereas MACS classifies
children based on their ability to handle objects in daily activities.
Procedure
Recruitment was undertaken through referral from treating clinicians (i.e. paediatricians,
physiotherapists, neuropsychologists, occupational therapists, speech therapists, and) from
the Queensland Paediatric Rehabilitation Service (QPRS); and state-wide outreach facilities.
All prospective participants were screened for study eligibility by a rehabilitation physician.
The GMFCS level was classified by the study Physiotherapist while MACS level was
determined by the study Occupational Therapist. After obtaining verbal consent, participants
were provided with study information and informed study consent was obtained.
RCT OF MITII FOR EF WITH ABI 5
All eligible children and adolescents were matched in pairs by age (within 18 month age
bands) and IQ (current within a two year period of recruitment based on the Wechsler
Intelligence Scale for Children – Fourth Edition; WISC-IV)20 and pairs were randomised to
20 weeks of Mitii™ training (immediate) or 20 weeks of Care As Usual (CAU; wait-list
control). Randomisation was undertaken by randomly allocating one member of each pair
either a “1” or “2” using a computer generated number table. Treatment allocations were
recorded on a piece of folded paper and assigned to consecutively numbered opaque
envelopes which were opened by independent non-study personnel. Treatment allocations
were recorded and study personnel informed.17
Study data were collected in a specially assigned multi-purpose clinic at The University of
Queensland, Brisbane. All participants were assessed over one or two days at the baseline
time-point (T1) and the post-intervention (i.e. after 20 weeks of Mitii™ training; T2) time-
point by an Occupational Therapist, Physiotherapist, and Neuropsychologist. A MRI
assessment was performed on participants who provided additional consent. The
neuropsychological assessment took approximately 1 to 2 hours with breaks when needed for
the baseline assessment and approximately 45 minutes to 1 hour for the post-intervention
follow-up appointment. Neuropsychological assessment was typically scheduled first, in
order to limit cognitive fatigue. After baseline testing, participants who were randomised into
the immediate Mitii™ training group spent an additional day at the clinic in order to be
trained by study personnel to use the Mitii™ program. These participants were provided with
the equipment needed to complete the Mitii™ program at home for the 20 week intervention
period. Equipment included a Microsoft Kinect®, with laptop and internet dongle or sim card
being provided to families who had limited access to a computer and internet at home.
Additional physiotherapy equipment including step blocks, wobble discs, and weights were
provided to all participants as these were integrated into the Mitii™ intervention. All
RCT OF MITII FOR EF WITH ABI 6
participants returned after 20 weeks for post-intervention assessments. Further details on the
study dose, intervention, content, and monitoring of study fidelity are provided in the study
protocol.17
Intervention
Each participant in the Mitii™ intervention group was provided training in order to learn how
to the use the Mitii™ program. A therapist explained to participant and parents the theoretical
background and purpose of the program. Families were given motivational strategies to
encourage child participation in the program, engaged in discussion about the need for
parental supervision, and provided with a demonstration of a generic program. The Mitii™
program is designed for a range of difficulty levels (i.e. easy, moderate, or difficult) and can
be configured to left, right or bimanually impaired function.17
Once the participant returned home, the therapists (i.e. one occupational therapist, one
physiotherapist, and one neuropsychologist) used the baseline assessment results to design an
individualised Mitii™ program suited to the needs and physical capabilities of the participant.
Therapists selected from the 11 available Mitii™ modules which included modules targeted
to (i) gross motor or physical activity (e.g. repetitive star jumps); (ii) combined cognitive and
visual perception (e.g. match the concepts); or (iii) upper limb (e.g. moving upper limb to
solve a mathematical problem). Modules were selected for an individualised program time of
30 minutes. All participants were encouraged to complete their programs six days a week,
which would provide the potential dose of 60 hours over the 20 week period. Programs were
designed to include 40% gross-motor and 60% cognitive-upper limb training modules.
All participants were provided with a de-identified Mitii™ account using an alias chosen by
them. Participants were required to download the Mitii™ program onto their home computers
or laptops provided by the researchers and login using their alias and a pre-determined
password. Therapists monitored participant’s weekly progress and updated the programs
RCT OF MITII FOR EF WITH ABI 7
weekly, increasing or decreasing intensity and/or changing the speed, accuracy and
repetitions of individual modules in order to maintain a just right level of challenge.
Participants and families were contacted regularly via phone or email by the therapists to
provide feedback and support.
Measures
Intellectual ability. Full Scale Intelligence Quotient (FSIQ) was calculated using the WISC-
IV20, consisting of the 10 subtests of Block Design, Similarities, Digit Span, Picture
Concepts, Coding, Vocabulary, Letter-Number Sequencing, Matrix Reasoning,
Comprehension, and Symbol Search. These subtests combine to create the four indices of
verbal comprehension (VCI), perceptual reasoning (PRI), processing speed (PSI), and
working memory (WMI). The FSIQ is generated from these four index scores. Internal
consistencies documented for the VCI, PRI, WMI, and FSIQ index scores of the WISC-IV
are excellent (r=0.92 - 0.97, averaged across all age groups).20 In addition, the PSI has good
internal consistency (r=0.88, averaged across all age groups).20
Executive functioning measures. All participants completed a neuropsychological test battery
consisting of subtests from the WISC-IV, Delis-Kaplan Executive Functioning System (D-
KEFS)21, Comprehensive Trail Making Test (CTMT)22, Tower of London (TOL)23, and Test
of Everyday Attention for Children (Tea-Ch)24 designed to measure the domains of EF as
outlined by Anderson’s (2002) paediatric model of EF. Measures were selected based on ease
of administration, documented test-retest reliabilities, and as these measures had been
previously used to assess Anderson’s EF domains in similar populations. The Behaviour
Rating Inventory of Executive Function (BRIEF)25 was also administered to parents or
guardians in order to assess everyday EF.
Attentional control. Attentional control was measured using Sky Search (SS; Tea-Ch), Score!
– number of trials correct (SCORE; Tea-Ch), Inhibition time of the Colour Word Interference
RCT OF MITII FOR EF WITH ABI 8
Test (CWI; D-KEFS), and Conditions 2 and 3 of the CTMT. Sky Search is a visual scanning
and focused attention task with good test-retest reliability (r=0.75).24 Due to the ceiling effect
in this test, test-retest correlations are not calculated however Score! is 76.2% in agreement
within one standard deviation for test-retest.24 The CWI Inhibition task has excellent test-
retest reliabilities (r=0.90, averaged across 8-19 year olds), and the internal consistency for
the CTMT Conditions 2 and 3 is between 0.69 and 0.74.21,22
Cognitive flexibility. Cognitive flexibility was measured using Digit Span Backwards (DSB;
WISC-IV), Sky Search Dual Task (SSDT; Tea-Ch), and Condition 4 and 5 of the CTMT. The
internal consistency for the Digit Span Backwards subtest is good (r=0.87, averaged across
all age groups).20 Sky Search DT has good test-retest reliability (r = 0.81) and the internal
consistency for Conditions 4 and 5 ranges from 0.68 to 0.69.22,24
Goal setting. Goal setting was measured using the Tower Of London where participants must
solve 10 problems increasing in difficulty. Test-retest reliability for the TOL ranges from
0.28 to 0.75.23
Information processing. The information processing domain was measured using WISC-IV
Coding and Symbol Search, and the colour naming, and word reading of the CWI test (D-
KEFS). Both Coding and Symbol Search have adequate to good internal consistency (r=0.82
and 0.79 respectively) and good test re-test reliabilities (r=0.81 and 0.80 respectively).20 Test-
retest reliabilities for the colour naming and word reading subtests are r=0.79 and r=0.77
respectively.21
EF in everyday life. To measure EF in everyday life, parents or guardians completed the
BRIEF, a parent rated questionnaire. For the current study, the Behavioural Regulation Index
(BRI) and the Metacognition Index (MCI) index scores were derived for the analyses. A
Global Executive Score (GEC) was also calculated, by combining BRI and MCI. All raw
scores were standardised using T-scores, with higher T-scores indicating more clinically
RCT OF MITII FOR EF WITH ABI 9
significant EF difficulties in everyday life. The BRIEF is a valid measure of EF and has good
to excellent internal consistency (r=0.80-0.97) and adequate to good test-retest reliabilities
(r=0.76-0.88).25
Other measured characteristics. Parents or guardians also completed questionnaires at both
assessment time-points. The baseline questionnaire detailed family characteristics (e.g.
marital status, family type, gross family income, and employment of parent), and whether or
not the child had any additional diagnoses (e.g. intellectual or learning disability, hearing or
vision impairment, Attention Deficit Hyperactivity Disorder, or epilepsy). Children were
classified according to the Australasian Rehabilitation Outcome Centre (AROC) impairment
codes.26 Parents of children in the Mitii™ intervention group were also interviewed by a
therapist using non-standardised acceptability and feasibility exit semi-structured
questionnaire upon completion of 20-weeks of Mitii™ training.27 Participation was voluntary
for all parents and no further incentive was offered.
Statistical methods
Summary statistics are reported as mean (± standard deviation) for continuous variables and
as frequency (percentage) for categorical variables. The association between treatment group
and EF outcome at 20 weeks was investigated using least squares linear regression, with
treatment group (standard care/Mitii™) included as the main effect. According to
CONSORT28 guidelines, analyses were conducted on an intention-to-treat basis which means
individuals were analysed in the group they were allocated to, regardless of treatment dose
received. Analyses were conducted using IBM SPSS version 22.00 (Statistical Package for
the Social Sciences v22).
Results
During the recruitment process, 534 individuals were screened for inclusion in the study with
77 children and adolescents meeting inclusion criteria and 60 providing consent. Children
RCT OF MITII FOR EF WITH ABI 10
were matched in pairs by age and IQ and were randomised to Mitii™ (immediate; n=30) or
waitlist control (n=30) as displayed in the CONSORT flow chart in Figure 1. Two
participants (one from each group) withdrew from the study before baseline assessments took
place. Baseline demographic, social, and clinical characteristics for the remaining 58
participants are presented in Table 1. Between groups differences were tested at baseline,
with no significant differences found between groups on demographic characteristics and
WISC-IV composite scores, p > 0.005 (VCI mean difference = -1.90, 95%CI -10.12,6.32,
p=0.27; PRI mean difference = -1.48, 95%CI -10.11,7.14, p=0.71; WMI mean difference = -
0.93, 95%CI -10.71,8.85, p=0.87; PSI mean difference = -5.10, 95%CI -14.38,4.25, p=0.62;
FSIQ mean difference = -2.07, 95%CI -10.94,6.81, p=0.87).
Intervention
Participants in the Mitii™ intervention group completed an average of 17.57 hours (SD
14.85) of Mitii™ total intervention, over the 20 weeks. The average minutes of training per
participant per week ranged from 0 to 46.14 hours. Four participants in the Mitii™
intervention group were unable to complete the Mitii™ intervention or attend post
intervention assessments at 20 weeks (retention 86%). Reasons for withdrawal included an
inability to be contacted by research personnel (n=1), decline to continue in the study (n=2),
and medical reasons (n=1). Three participants in the waitlist (control) group withdrew from
the study and did not attend post intervention assessments at 20 weeks (retention 89%).
Primary outcomes
Outcomes for baseline and 20-week for the Mitii™ intervention group and wait-list control
groups are presented in Table 2. There were no significant differences at 20 weeks in EF
capacity for children in the Mitii™ intervention group as compared to children in the control
(waitlist) group on all measures of EF performance; Digits span Backwards (p=0.17; CI=-
2.23-2.21); Symbol Search (p=0.10; CI=-1.16-2.53); Coding (p=0.80; CI=-1.78-1.59);
RCT OF MITII FOR EF WITH ABI 11
CTMT Trail 2 (p=0.98; CI= -7.33-7.09); CTMT Trail 3 (p=0.56; CI=-5.93-9.61); CTMT
Trail 4 (p=0.10; CI= -6.40-9.12); CTMT Trail 5 (p=0.44; CI= -4.87-7.91); CWI Colour
Naming (p=0.80; CI=-1.95-2.28); CWI Word Reading (p=0.80; CI=-1.95-2.28); CWI Colour
Naming (p=0.80; CI=-1.95-2.28); TOL Total Correct (p=0.10; CI =-6.92-7.65); TEA-Ch
SkySearch (p=0.68; CI=-2.17-1.34); TEA-Ch Score! (p=0.91; CI=-1.30-2.93); and TEA-Ch
SkySearch DT (p=0.52; CI=-2.87-0.74) using linear regression analysis.
Secondary outcomes
Similarly, there were no between group differences observed at 20 weeks for measures of EF
performance as measured by the BRIEF: BRIEF GEC (p=0.66; CI =-7.27-5.36); BRIEF BRI
(p=0.62; CI =-9.44-6.51); and BRIEF MI (p=0.69; CI =-6.10-5.41).
As treated analysis
A post-hoc per protocol analysis indicated a significant and large effect of CTMT Colour
Naming subtest scores on dose levels, F(2,46)=5.54, p=0.007, ω=0.40, when separated into
care as usual (wait-list control group, M=6.92, SD=3.84, SE=0.77), less than 15 hours of
training (M=5.00, SD=3.03, SE=0.84), and more than 15 hours of training (M=9.55,
SD=2.21, SE=0.67). Pairwise comparisons corrected using Tukey revealed a significant
linear trend between training for more than 15 hours and training for less than 15 hours (mean
difference = 4.55; p=0.005) with better performance on Colour Naming for those who trained
for more than 15 hours. A trend towards significance was also found on Colour Naming
performance for those with more than 15 hours training compared to those who received care
as usual (mean difference = 2.63; p=0.09). No significant trend was observed between
training for less than 15 hours and care as usual on the Colour Naming subtest (mean
difference = -1.92; p>0.05). No additional dose effects were observed across measures of EF.
Acceptability and feasibility semi-structured questionnaire
RCT OF MITII FOR EF WITH ABI 12
Parents of children in the intervention group (n=21/25) reported they were satisfied with
Mitii™ and the quality of the program, and were satisfied with the support and help provided
by the research team. Parents reported that the Mitii™ program helped somewhat with
improving their child’s performance at school; problem-solving, decision-making, and
organisational skills; and somewhat helped their child improve his/her self-esteem. Positive
aspects of the program included the use of intensive therapy and flexibility of accessing the
program at home. Negative aspects of the program included lack of motivation and time
constraints, and problems with accessibility and program errors.
Discussion
This randomised controlled trial evaluating the efficacy of a novel, internet-based, multi-
modal rehabilitation program found no significant differences between Mitii™ and Care as
Usual after 20-weeks on all measures of executive functioning. While the current results are
non-significant, poor program adherence consequently prevents us from disconfirming our
hypotheses that 20 weeks of multi modal training Mitii™ would significantly improve EF
abilities and performance in children and adolescents with ABI. Participants assigned to the
intervention group did not meet the proposed training dose of 60 hours. The dose varied with
an average of 17.6 hours, substantially less than the dosage achieved by children with UCP in
previous studies.15,29 When considering dose effects, participants in the Mitii™ intervention
group who trained for more than 15 hours showed significant improvements in the Colour
Naming subtest of the D-KEFS when compared to those who trained for less than 15 hours.
No other dose effects were observed. This ultimately undermines the premise of the program
which is to provide rehabilitation that is intensive and repetitive in order to drive
neuroplasticity. The current dosage reached 28% of the planned dosage level, potentially
preventing meaningful EF changes. A similar effect was found across the larger RCT with
children in the intervention group having statistically significant changes in visual figure
RCT OF MITII FOR EF WITH ABI 13
ground on an occupational measure30 and an increase in functional strength on lower limbs27
however these were not considered to be clinically significant. No other secondary outcomes
reported significant improvements between groups on Occupational Therapy or
Physiotherapy for this cohort.27,30
The reduced level of adherence found in the current study may be attributed to a number of
factors and comorbidities. As indicated in the Acceptability and Feasibility exit semi-
structured questionnaire, most parents reported experiencing difficulties with internet
connectivity, lengthy download delays, and software glitches. While technical support from
therapists and telemedicine engineers were utilised by families, the home-delivered nature of
the program meant families had to have some degree of technical knowledge to troubleshoot
problems with the software. Unfortunately, some technical difficulties prevented logins
which then increased frustration and prompted disengagement from the program. Adherence
may have been confounded by fatigue and lack of concentration and attention, comorbidities
often reported in this cohort of children with ABI.31 Parents additionally reported a lack of
engagement, with suggestions of providing more choice in modules contextualised to
Australian children and adolescents, and the need for more supervision of home participation
within Mitii™.
The Mitii™ program was designed to improve upper limb functioning, together with physical
strength and visual perceptual skills. Modules in the program that were cognitive in nature
(e.g. mathematics, matched pairs and memory) were a smaller percentage of the total games
compared to the visual perception and physical activity games (i.e. less than 20%). The
cognitive component of the training may not have been sufficient to drive changes in EF. In
order to improve EF the program may have needed more specific training in EF areas. Many
of the visual perceptual and upper limb modules required attentional control, speed of
information processing and cognitive switching, however the modules did not target goal-
RCT OF MITII FOR EF WITH ABI 14
setting, more complex problem solving, nor require intense mental flexibility and fast
cognitive switching. Furthermore, EF relies on the novelty of activities and for problems to
be complex. The nature of repetitive training may not allow for these factors.
Mitii™ is an individualised program. There are limitations to what parameters can be
changed and at times the program was too easy for the participant. There were also times that
the participant was unable to complete tasks due to their complexity and the supervision
required. There needs to be consideration for the age of the client, their motivation,
engagement and the development of their EF skills. Executive functioning abilities develop at
different ages and often have different trajectories dependent on neurophysiological
development32,33. Future interventions should consider family factors and the child’s
behaviour which may impact their engagement with therapy in the home environment.
The current study, though not successful in terms of demonstrating an effect on brain
training, has multiple strengths in this area where there has been a paucity of research.13,14 The
study has a large sample size of participants with ABI and high retention rates (87%). The
matched pair design limited group differences at baseline and the methodology followed
CONSORT Guidelines. To our knowledge, this is the first large randomised control trial to
assess a multi-modal online intervention for children with ABI. Future research would benefit
from employing this rigorous research design to test the effectiveness of interventions for
children with ABI. Online interventions are increasingly important to deliver services to rural
and remote families, as well as providing families with intensive interventions they can
complete in their home environment. Online interventions also have the capacity to be
delivered within a school setting and so can be a flexible method of delivering much needed
intervention following the acute phase of rehabilitation. Interventions which are specific to
EF and that are contextually based may have the ability to improve EF skills. In its current
form, Mitii™ is not effective in improving EF in children with an ABI with varying levels of
RCT OF MITII FOR EF WITH ABI 15
function. Future research should examine the efficacy of specific interventions for EF
functioning and their generalizability to real world situations.
Clinical messages
Poor program adherence lead to non-significant findings after evaluating the efficacy
of Mitii™, a novel, web-based, multi-modal rehabilitation program.
Web-based programs need to be designed to accommodate a number of key factors
identified in the current study that contributed to poor program compliance.
RCT OF MITII FOR EF WITH ABI 16
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based multimodal therapy for children with acquired brain injury to improve gross
motor capacity and performance. Clin Rehabil. 2016.
RCT OF MITII FOR EF WITH ABI 19
28. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: Updated
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web-based rehabilitation on occupational performance and upper limb outcomes:
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life 13 years after traumatic brain injury in childhood. International journal of
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tests of purported frontal love functioning. Dev Neuropsychol 1991;7:377-395.
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Neuropsychol 1991; 7: 131-149.
RCT OF MITII FOR EF WITH ABI 20
Table 1. Participant demographics and baseline characteristics of Mitii™ and Control Groups
Characteristics Mitii™ ™ (n=29) Control group
(n=29)
Age, mean (SD) 11y, 10m (2y, 6m) 11y, 11m (2y, 6m)
Age of injury, mean (SD) 5y, 9m (3y, 5m) 5y, 2m (4y)
Gender, male n (%) 15 (51.7%) 17 (58.6%)
MACS n (%)
Level I 15 (51.7%) 17 (58.6%)
Level II 12 (41.4%) 12 (41.4%)
Level III 2 (6.9%) 0 (0%)
GMFCS n (%)
Level I 12 (41.4%) 17 (58.6%)
Level II 17 (58.6%) 12 (41.4%)
Epilepsy 6 (20.7%) 3 (10.3%)
AROC codes
Stroke Haemorrhagic
Left body involvement (1.11) 3 1
Right body involvement (1.12) 1 4
Bilateral involvement (1.13) 1 1
Other (1.19) 1 0
Stroke Ischaemic
Left body involvement (1.21) 2 3
Right body involvement (1.22) 1 3
RCT OF MITII FOR EF WITH ABI 21
Bilateral involvement (1.23) 1 0
Brain dysfunction, non-traumatic
Other (2.13) 8 9
Brain dysfunction, traumatic
Open injury (2.21) 1 1
Closed injury (2.22) 10 7
Intellectual disability
FSIQ <80 below average (%) 4 (14%) 7 (25%)
Other diagnoses n (%)
Learning disorder 16 (55.2%) 13 (44.8%)
Hearing impairment 1 (3.5%) 0 (0%)
Vision impairment 7 (24.1%) 11 (37.9%)
ADHD 1 (3.5%) 3 (10.3%)
Autism spectrum disorder 1 (3.5%) 2 (6.9%)
VCI (WISC-IV) 82.57 ± 13.03 (n = 28) 83.24 ± 16.76
PRI (WISC-IV) 78.93 ± 16.77 80.41 ± 16.01
WMI (WISC-IV) 79.79 ± 16.76 80.72 ± 20.06
PSI (WISC-IV) 72.24 ± 18.09 77.31 ± 17.32
FSIQ (WISC-IV) 75.36 ± 14.77 (n = 28) 76.24 ± 17.84
Family type, n (%)
Original 18 (62.1%) 18 (62.1%)
Step-family 5 (17.2%) 3 (10.3%)
Sole parent 5 (17.2%) 7 (24.1%)
Other 1 (3.5%) 1 (3.5%)
RCT OF MITII FOR EF WITH ABI 22
Key: MACS = Manual ability level; GMFCS = Gross motor function classification scale; AROC = Australasian
Rehabilitation Outcome Centre; ADHD = Attention deficit/hyperactivity disorder; WISC-IV = Wechsler
Intelligence Scale for Children – Fourth Edition; FSIQ = Full scale intellectual Quotient; VCI = Verbal
Comprehension Index; PRI = Perceptual Reasoning Index; WMI = Working Memory Index; PSI = Processing
Speed Index
RCT OF MITII FOR EF WITH ABI 23
Table 2. Differences between Measures of Executive Functioning at baseline and 20 week follow up for Mitii™ and control groups (Mean ± SD)
Outcome Measure Mitii™ Intervention (n=29) Waitlist Control (n=29) MD 95% CIp
value
nBaseline mean
(SD)n
20 weeks
mean (SD)n
Baseline mean
(SD)n
20 weeks mean
(SD)
Digit Span
Backwards (WISC-
IV)
29 7.17±2.95 25 7.80±3.00 28 7.10±4.02 27 7.81±4.67 -0.01 -2.23,2.21 0.17
Symbol Search
(WISC-IV)29 5.66±2.79 25 7.72±2.82 25 7.72±2.82 26 7.04±3.66 0.68 -1.16,2.53 0.10
Coding (WISC-IV) 29 5.14±2.86 25 6.44±2.99 29 5.76±3.01 26 6.54±3.00 -0.10 -1.78,1.59 0.80
CTMT Trail 2 28 31.10±11.78 25 36.56±12.98 28 32.50±14.31 25 36.68±12.36 -0.12 -7.33,7.09 0.98
CTMT Trail 3 28 31.79±11.33 25 37.36±13.37 28 33.14±13.43 25 35.52±13.96 1.84 -5.93,9.61 0.56
CTMT Trail 4 28 30.71±7.45 25 35.60±10.89 28 30.18±13.27 25 34.24±15.92 1.36 -6.40,9.12 0.10
CTMT Trail 5 28 33.96±9.53 25 38.84±10.41 27 33.70±11.37 25 37.32±12.00 1.52 -4.87,7.91 0.44
Colour Naming (D- 28 6.71±3.53 24 7.08±3.50 29 4.69±3.99 25 6.92±3.84 0.16 -1.95,2.28 0.80
RCT OF MITII FOR EF WITH ABI 24
KEFS: CWI)
Word Reading (D-
KEFS: CWI)27 6.74±4.13 24 6.92±3.65 28 5.50±4.20 25 6.52±4.21 0.40 -1.87,2.67 0.25
Inhibition (D-KEFS:
CWI)27 6.70±3.48 24 8.83±3.38 28 7.07±3.53 25 7.72±3.47 1.11 -0.86,3.08 0.92
TOL Total Correct
Score28 91.50±18.80 25 93.32±14.56 26 102.31±11.01 26 95.62±20.13 0.37 -6.92,7.65 0.10
TEA-Ch Sky Search 29 6.41±2.93 25 7.24±2.96 28 6.57±3.29 26 7.65±3.26 -0.41 -2.17,1.34 0.68
TEA-Ch Score 28 7.42±3.85 24 8.38±3.67 29 6.28±3.71 25 7.56±3.70 0.82 -1.30,2.93 0.91
TEA-Ch SkySearch
DT27 4.26±3.91 24 4.46±2.99 28 4.18±3.53 25 5.52±3.27 -1.06 -2.87,0.74 0.52
BRIEF BRI 28 63.25±13.71 24 62.38±12.68 29 62.83±19.05 25 63.84±14.91 -1.47 -9.44,6.51 0.62
BRIEF MI 28 66.96±11.11 24 64.83±10.11 29 66.00±9.78 25 65.16±9.84 -0.33 -6.10,5.41 0.69
BRIEF GEC 28 66.79±12.02 24 65.00±11.06 29 66.69±11.72 25 65.96±10.91 -0.96 -7.27,5.36 0.66
RCT OF MITII FOR EF WITH ABI 25
Key: WL = Wait-list; WISC-IV = Wechsler Intelligence Scale for Children – Fourth Edition; CTMT = Comprehensive Trail Making Test; D-KEFS = Delis-Kaplan
Executive Function System; TOL = Tower of London; CWI = Colour Word Interference; TEA-Ch = Test of Everyday Attention for Children; BRIEF = Behaviour Rating
Inventory of Executive Functioning; BRI = Behaviour Regulation Index; MI = Metacognition Index; GEC = Global Executive Composite
* Cumulative Percentage
Table 3. Mitii™ Acceptability and Feasibility Parent-report Questionnaire at 20 weeks
(n=21)
Questions Response
Mean (SD)
Satisfaction with the program
1= Very dissatisfied; 5 = Quite satisfied; 9 = Very satisfied
How satisfied were you with the Mitii™ program that you and your
child received?
7.24 (1.61)
How satisfied were you with the quality of Mitii™ your child
received?
6.95 (1.28)
How would you rate support your child received during the Mitii™
training from the Mitii™ team?
7.95 (1.47)
How satisfied were you with the type of help received from the
Mitii™ program?
8.19 (1.03)
How satisfied were you with the amount of therapy you and your
child received with the Mitii™ program?
7.67 (1.68)
How satisfied were you with the amount of technical help and
support with the Mitii™ program you and your child received? eg.
fixing IT issues
7.33 (1.98)
How satisfied were you accessing therapy using an on line therapy
program?
7.33 (2.06)
Amount of therapy
1 = Less than usual; 5 = Same as usual; 9 = Much more than usual
Compared to the usual amount of therapy you receive, can you rate
the amount of therapy you think the Mitii™ program offered
7.91 (1.48)
Meeting your needs
RCT OF MITII FOR EF WITH ABI 27
1=Not net at all; 5 = Needs somewhat met; 9 = All needs met
To what extent has the program met your child’s needs? 6.95 (1.77)
Program Duration
1 = Much too long; 5 = Just Right; 9 = Much too Short
Please comment on the overall length (20 weeks) 5.05 (1.94)
Please comment on the frequency (up to daily) 4.52 (0.93)
Please comment on the daily duration (20-30 minutes) 4.76 (0.77)
Reported improvements
1 = Hasn’t helped at all; 5 = Helped Somewhat; 9 = Helped a lot
Has the Mitii™ program helped your child perform better at
school?
5.71 (2.51)
Has the Mitii™ program helped your child’s problem-solving,
decision-making, or organisational skills?
5.29 (2.49)
Has the Mitii™ program helped your child improve his/her self-
esteem?
5.19 (2.54)
RCT OF MITII FOR EF WITH ABI 28
Figure 1: Neuropsychology Consort flow chart
Databases (n= 531)
Excluded (based on chart review), not meeting inclusion criteria
(n= 382)
Primary outcome post-intervention completion (n=51) (T1)
20 weeks
Waitlist (n= 29)Care as usual, Regular OT/PT
(amount and contact monitored)
Matched and Randomized (n= 60)
Self-contact or other referrals (n= 3)
Immediate (n= 29)20 weeks MitiiTM training
(70 Hours multi-modal training)
Baseline T0 Assessments (n= 58)
0 weeks
Baseline Measures (T0)Classification: AROC codes, MACS, GMFCS, Height, WISC-IV Full Scale Intelligence Quotient (n = 57)Colour-Word Inference Test (D-KEFS; n = 55)Comprehensive Trail Making Test (n = 55)Tower Test (n = 54)Score! (TEA-Ch; n = 57); Score DT (TEA-Ch; n = 55)Sky Search (TEA-Ch; n = 57)BRIEF (n = 57)Strengths and Difficulties Questionnaire (SDQ; n = 53)
Post Intervention Outcomes (T1)Classification: AROC codes, MACS, GMFCS, Height, WISC-IV Digit Span (WISC-IV; n = 49)Symbol Search (WISC-IV; n = 48); Coding (WISC-IV; n = 49)Colour-Word Inference Test (D-KEFS; n = 47)Comprehensive Trail Making Test (n = 48)Tower Test (n = 49)Score! (TEA-Ch; n = 47); Score DT (TEA-Ch; n = 47)Sky Search (TEA-Ch; n = 49)BRIEF (n = 48)Strengths and Difficulties Questionnaire (SDQ; n = 46)
2 failed to proceed (Subject #41 & #49)
Contacted (n= 77)
Recruitment finalised before contacted/chart reviewed (n= 75)
Excluded:- Declined to participate (n= 15)- Ineligible based on phone review
(n= 2)
Enro
llmen
tA
lloca
tion
3 Dropouts (Subject #51, #59, #46
4 Dropouts (Subject #42, #52, & #53,
#60)
RCT OF MITII FOR EF WITH ABI 29
Figure 1 legend
AROC- Australasian Rehabilitation Outcomes Centre. MACS- Manual Ability Classification
System. GMFCS- Gross Motor Function Classification System. 6MWT- Six Minute Walk
Test. HiMAT- High Level Mobility Assessment Tool. TUG- Timed Up and Go. WISC-IV-
Wechsler Intelligence Scale for Children IV.