Early Training of Attention After Acquired Brain Injury
Condition: Traumatic Brain Injury; Stroke
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Interventional

Summary: 
      Background: To study intensive targeted cognitive rehabilitation of attention in the acute
      (<4 months) and subacute rehabilitation phases (4 -12 months) after acquired brain injury and
      to evaluate the effects on function, activity and participation (return to work).

      Design: prospective, randomised, controlled study. Methods: 120 consecutive patients with
      stroke or traumatic brain injury are randomised to 20 hours of intensive attention training
      by Attention Process Training or by standard, activity based training. Progress is evaluated
      by Statistical Process Control and by pre and post measurement of functional and activity
      levels. Return to work is also evaluated in the post-acute phase. Primary endpoints are the
      changes in the attention measure, Paced Auditory Serial Addition Test and changes in work
      ability. Secondary endpoints include measurement of cognitive functions, activity and work
      return. There are 3, 6 and 12-month follow ups focussing on health economics.

      Discussion: The study will provide information on rehabilitation of attention in the early
      phases after acquired brain injury (ABI); effects on function, activity and return to work.
      Further, the application of Statistical Process Control might enable closer investigation of
      the cognitive changes after acquired brain injury and demonstrate the usefulness of process
      measures in rehabilitation.
    

Detailed description: 
      STUDY METHODS The primary objectives of the study were: 1. In the acute stage, to evaluate
      the effectiveness of APT measured by the changes in performance in the attention measure,
      Paced Auditory Serial Addition Test, (PASAT) evaluated by Statistical Process Control 2. In
      the postacute stage, to evaluate and compare effects of Attention process training (APT) vs.
      standard rehabilitation on daily activities and return to work three months and one year
      after participating in a rehabilitation programme with regard to resource utilisation and
      health economics.

      STUDY DESIGN AND SETTING The study was conducted in a specialised rehabilitation clinic.
      Several in- and outpatient units on two sites were involved. It was a randomised, controlled
      (www.consort-statement.org/?o=1011) study with an open extension and a follow up at three and
      six months and one year. Due to the nature of the rehabilitation procedures, neither patients
      nor rehabilitation professionals were blinded as to the nature of the intervention, but
      different professionals conducted assessments and training. The study was designed to reflect
      normal clinical practice while allowing comparison between two rehabilitation approaches.
      Patients in the acute phase (< 4 months) were recruited from both in- and outpatient units.
      For those, ready to be discharged from inpatient wards, the training was continued in the
      outpatient setting. Subacute patients (4-12 months) participated in the study as part of
      their outpatient rehabilitation. The study was approved by the regional ethics committee,
      Karolinska Institutet, Stockholm, Sweden.

      The participants comprised a consecutive series of patients with mild to moderate stroke or
      traumatic brain injury. Inclusion criteria were deficits in attention defined by the APT
      test, scores on the lower average and above for reasoning skills and abstract thinking, age
      range; 18-60 years and a good understanding of the Swedish language. Exclusion criteria were
      moderate to severe aphasia, ongoing psychiatric illness, a history of severe somatic disorder
      causing anoxic periods, ongoing substance abuse and severe pain. Patients with Hospital
      Anxiety and Depression Scale scores =>10 were offered antidepressant treatment and were
      included in the study three weeks after pharmacological treatment had been initiated.
      Further, exclusion was also based on severe memory disorders, neglect, visual field defects
      and motor disability interfering with participation.

      All patients participated in a comprehensive interdisciplinary brain injury rehabilitation
      programme. After baseline assessment, the participants received 20 hours of attention
      training, at least three days a week, for a period of 5-6 weeks. They were randomly assigned
      to one of the two intervention programmes: intensive area-specific cognitive training with
      the APT or activity-based attention training provided by the occupational therapist.
      Evaluation of treatment effects was monitored by pre and post assessment and by repeated
      assessment by the primary outcome measure at baseline, after every third hour of intervention
      and post intervention for patients in the acute stage. Subacute patients were assessed by pre
      and post measurements. The open-label extension of the study comprised of client-centred
      standard interdisciplinary rehabilitation. Discharge was based on clinical decisions and the
      participants returned to the clinic for follow-up assessments.

      The APT programme provides a theoretically based, individualised, highly structured
      intervention of organised assignments at four attention levels: sustained, selective, divided
      and alternating attention. Progress is based on the intensity of training, on continuous
      feedback promoting motivation and on metacognitive training. The APT also includes education
      in acquired attention deficits and training for generalisation, enabling the transfer of
      treatment tasks and techniques to self-selected cognitive problems in everyday situations.
      Each session took 45-90 minutes to perform, working with material from APTs I and II.

      Attention training in activities included standard occupational training within an
      interdisciplinary rehabilitation programme. The programme consisted of a) training and the
      use of compensatory strategies in attention-demanding activities of daily living b)
      performing independent work with attention-demanding tasks at individual level c) training
      using computerised tasks, not specifically designed for attention remediation and d) group
      activities. Types of training and time devoted to a specific training procedure were
      individually registered.

      Inclusion measures were the APT-test and Matrix reasoning.Cut-off scores were 70% or less on
      at least two of the five subtests on the APT-test and standard scores of seven and above on
      Matrix Reasoning.

      Exclusion measures were Barthel Activity of Daily Living, (ADL)-index 50 or less; Alberts
      test/Line crossing with a cut off score of (<=2); and a profile score of seven or less for
      The Rivermead Behavioural Memory Test.

      Primary outcome measures: For the acute phase: The Paced Auditory Serial Addition test,
      (PASAT) is presumed to measure working memory speed of information processing and sustained
      and divided attention. Versions A and C were administered.

      For the subacute phase the primary outcome measurement was the Work Ability Index (WAI).

      Secondary outcome measures were functional, activity and participation measures. Further
      measures of attention were the Digit Span task, the Block Span, the Ruff 2&7 Selective
      Attention Test ,and the Letter-Number Sequencing task.

      For executive measures the Trail Making Test, the Color-Word Interference Test and the Tower
      Test were used. The latter is administered only once due to learning effects, thus allowing
      only group comparisons. The Rey Auditory Verbal Learning Test (RAVLT) has been used to
      evaluate different aspects of memory function.

      Depression and anxiety were assessed by the Hospital Anxiety and Depression Scale (HADS).

      Activity measures were the Cognitive Failure Questionnaire, the Rating Scale of Attentional
      Behavior and the Dysexecutive symptom questionnaire. Occupational Performance was measured by
      the Canadian Occupational Performance Measure (COPM).

      Participation and work-return measures were the Work Ability Index, used to assess self-rated
      work ability. The Assessment of Work Performance used to assess the skills of clients with
      various work-related problems during their work performance and the Work Ability Screening
      Questionnaire constructed by the authors including questions about education, current
      profession, work situation, current work ability, and approach to future work ability and
      return to work questions.

      Adverse effects were registered in field notes and standard hospital journals. Examples of
      adverse effects were: fatigue preventing participation in APT training, negative effects of
      the APT treatment, such as consequences of fatigue on following treatments, sudden emergence
      of exclusion criteria, etc.

      To assess resource utilisation and economic evaluation data for work capacity/sick leave
      before, and 12 months after ABI were obtained from the Registry for the Swedish Social
      Insurance Agency. For data regarding utilisation of health services related to ABI and
      medical and physical interventions, the participants were contacted by phone 12 months after
      injury. Resource utilisation was defined as the use of health care and social services
      associated with ABI. Costs of resources were calculated from a societal perspective, i.e.
      costs within the health-care system, transport, and caregiver's time and for sick leave.
      Patients' and caregivers' lost productivity was calculated based on productivity data from
      before ABI.

      The sample size calculation for the primary endpoint was based upon the estimate of 1
      standard deviation (SD) improvement after 20 hours of attention training with APT or
      activity-based attention training. Setting an alpha at 0.05, with a power of 85%, a sample
      size of 19 completed data sets was needed to detect a statistically significant difference
      between treatment arms. Assuming a dropout rate of 25% requires the inclusion of 25 patients.
      Sample size calculation for secondary endpoint goals on functional level was based upon the
      assumption of a clinically relevant change of 1 SD in the Ruff 2&7 test. For this effect
      size, a sample size of 30 complete data sets in each treatment arm, and alpha 0,0050,
      2-tailed, yields a power of 0.888. Sample size calculation on activity level was based upon
      the assumption of a clinically relevant (2-point) change in the COPM performance measure. For
      this effect size, a sample size of 30 complete data sets in each treatment arm, and alpha
      0,0050, 2-tailed, yields a power of 0.988. Thus the maximum number of patients to be enrolled
      was 120.

      The primary outcome measure was analysed by using statistical process control (SPC). Sigma
      Zone SPC, was used to explore statistical control limits and variability in improvement
      assuming that data plots appearing within the control limit indicate a process in stable
      statistical control and variations are due to chance variations, day-to-day variability in
      behaviour etc. Data were presented on control charts, including three additional lines; the
      centre line (usually based on the mean) and an upper (UCL) and lower control limit (LCL) set
      at ±3 standard deviations from the mean respectively). Data points outside those control
      limits are considered to be related to special causes of variation, such as effects of
      treatment. The Minimal Clinically Important Difference (MCID) in the primary outcome
      variable, PASAT was estimated and expressed as the minimum change of the PASAT-diff score
      that could be considered clinically relevant.

      Parametric methods, Student's t-test and Pearson correlation were used for normally
      distributed variables on interval level. When comparing the two treatment groups, t-tests for
      independent samples were used and for comparison between pre- post and follow up measures
      t-tests for dependent samples and analysis of variance were used. Skewed or ordinal data were
      analysed by non-parametric methods: Mann-Whitney U-test for comparison between the treatment
      groups; Wilcoxon matched pairs test, Kruskal-Wallis analysis of variance for comparison of
      pre- post and follow up measures and Spearman's rank correlation test. For post-hoc
      comparisons we used the Mann-Whitney U-test. Fisher's exact test was used for comparison
      between dichotomized variables. Bonferroni corrections were applied to correct for false
      positives due to the number of analyses. The possible effects of randomisation bias were
      investigated using a linear mixed-model analysis including one within-group factor treatment
      and one between-group factor. Cluster analysis was used for the primary outcome measure to
      explore and identify patterns of cognitive recovery in the acute phase.

      Two-tailed p-values were used with a critical significance level of 0.05. Health economics
      resource utilisation was calculated for each treatment arm for participants in both acute and
      subacute phases.
    

Intervention name(s): APT training; Multiprofessional rehabilitation
Intervention type(s): Behavioral; Behavioral
Intervention description(s): APT training was used as intensive area-specific cognitive training at four levels: sustained, selective, divided and alternating attention. The APT also includes education in acquired attention deficits and training for generalization. Each session took 45-90 minutes to perform. The APT-test was used to determine the level of difficulty for the attention training.; Attention training in activities included standard occupational training within an interdisciplinary rehabilitation programme. The programme consisted of training and the use of compensatory strategies in attention-demanding activities of daily living, performing independent work with attention-demanding tasks at individual level and group activities
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Brain injury; stroke; cognitive rehabilitation