Novel interdisciplinary intervention, GAIN, vs. enhanced usual care to reduce high levels of post-concussion symptoms in adolescents and young adults 2-6 months post-injury: A randomised trial

Mille Moeller Thastum, Charlotte Ulrikka Rask, Erhard Trillingsgaard Næss-Schmidt, Astrid Tuborgh, Jens Sondergaard Jensen, Susanne Wulff Svendsen, Jørgen Feldbæk Nielsen, Andreas Schröder, Mille Moeller Thastum, Charlotte Ulrikka Rask, Erhard Trillingsgaard Næss-Schmidt, Astrid Tuborgh, Jens Sondergaard Jensen, Susanne Wulff Svendsen, Jørgen Feldbæk Nielsen, Andreas Schröder

Abstract

Background: Evidence for effective interventions to prevent long-term sequelae after concussion is sparse. This study aimed to test the efficacy of Get going After concussIoN (GAIN), an interdisciplinary, individually-tailored intervention of 8 weeks duration based on gradual return to activities and principles from cognitive behavioural therapy.

Methods: We conducted an open-label, parallel-group randomised trial in a hospital setting in Central Denmark Region. Participants were 15-30-year-old patients with high levels of post-concussion symptoms (PCS) 2-6 months post-concussion (i.e., a score ≥20 on the Rivermead Post-concussion Symptoms Questionnaire (RPQ)). They were randomly assigned (1:1) to either enhanced usual care (EUC) or GAIN+EUC. Masking of participants and therapists was not possible. The primary outcome was change in RPQ-score from baseline to 3-month FU. All analyses were done on an intention-to-treat basis using linear mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT02337101.

Findings: Between March 1, 2015, and September 1, 2017, we included 112 patients. Patients allocated to GAIN+EUC (n=57) reported a significantly larger reduction of PCS than patients allocated to EUC (n=55) with a mean adjusted difference in improvement of 7·6 points (95% confidence interval (CI) 2·0-13·1, p=0·008), Cohen's d=0·5 (95% CI 0·1-0·9). Number needed to treat for prevention of one additional patient with RPQ ≥20 at 3-month FU was 3·6 (95% CI 2·2-11·3). No adverse events were observed.

Interpretation: Compared with EUC, GAIN+EUC was associated with a larger reduction of post-concussion symptoms at 3-month FU.

Funding: Central Denmark Region and the foundation "Public Health in Central Denmark Region - a collaboration between municipalities and the region".

Keywords: Brain concussion; Cognitive behavioural therapy; Graded exercise therapy; Illness perceptions; Intervention; Mild traumatic brain injury; Post-concussion syndrome; Rivermead Post-Concussion Symptoms Questionnaire.

Conflict of interest statement

None.

© 2019 Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
CONSORT flowchart and timeline of assessments. The timeline represents median time in months after concussion at the three assessment points, with 0 being the time of injury. Baseline: 3·7 months (range 2·1–7·1 / IQR 3·1–4·6); EOI: 7·5 months (range 4·1–12·1 / IQR 6·5–8·8); 3-month FU: 10·6 months (range 6·9–15·6 / IQR 9·5–11·9). aOther reasons” includes: not from Central Denmark Region; previous concussion within 2 years leading to previous or ongoing post-concussion symptoms lasting ≥3 months; signs of more severe brain injury; time since injury >6 months; other severe psychiatric or somatic disease; going abroad; unable to communicate in Danish. b Due to a protocol violation one patient diagnosed with bipolar disorder was erroneously randomised to EUC and excluded after inclusion (i.e., 113 patients were randomised). c Violation of procedure: seven patients from EUC did not receive questionnaires at EOI on December 18, 2017, as planned due to an error in the database. This was not realised until 3-month FU. Abbreviations: EOI = end of intervention; EUC = enhanced usual care; FU = follow-up; GAIN = Get going After concussIoN; GP = general practitioner; ITT = intention-to-treat; IQR = interquartile range.
Fig. 2
Fig. 2
Change in RPQ total score and RPQ subscales (unadjusted mean, 95% CI), (n = 112). The x-axis represents median time in months after concussion at the three assessment points (baseline; end of intervention; 3-month follow-up). The reference line on (A) indicates the a priori defined cut-off for a high level of post-concussion symptoms (RPQ ≥20), i.e., the cut off for inclusion in the study. RPQ total score = primary outcome. RPQ subscales = post-hoc analysis. P-values are based on an unadjusted linear mixed model. d = Cohen's d (95% CI) at 3-month FU. Abbreviations: EUC = enhanced usual care; GAIN = Get going After concussIoN; RPQ = Rivermead Post-Concussion Symptoms Questionnaire.
Fig. 3
Fig. 3
Change in treatment target measures and secondary outcomes (unadjusted mean, 95% CI), (n = 112). The x-axis represents median time in months after concussion at the three assessment points (baseline; end of intervention; 3-month follow-up). P-values are based on an unadjusted mixed model and pertain to change between baseline and 3-month follow-up. (A), (B), (C), (G), and (H): higher scores indicate more symptoms/worse function. (D), (E), and (F): higher scores indicate less symptoms/better function. (A)–(D): the sum was transformed into a 0–100 scale according to the questionnaire manuals. (E) and (F): SF-36 subscales were converted to T-scores based on US normative data. The reference line at T= 50 shows the US population mean. * The SCL-8 analysis was performed on the subgroup of patients with an SCL-8 dichotomised score ≥5 at baseline (n = 41) . Abbreviations: B-IPQ = Brief Illness Perception Questionnaire; BRIQ = Behavioural Response to Illness Questionnaire; EUC = enhanced usual care; GAIN = Get going After concussIoN; QOLIBRI-OS = Quality of Life after Brain Injury – Overall Scale; SCL-8 = Symptom Checklist-8; SF-36 = Short Form 36 Health Survey (pcs = physical component summary, mcs = mental component summary).
Fig. A1
Fig. A1
Post-concussion symptoms: change in single RPQ items. The graphs show the mean score on each RPQ item at each assessment point in GAIN+EUC and EUC for those patients, who reported a score ≥2 on the respective RPQ item at baseline (= n displayed on each graph). Patients are asked how much they suffer from each symptom now compared with before the injury. Response categories: 0 = not experienced at all; 1 = no more of a problem; 2 = a mild problem; 3 = a moderate problem; 4 = a severe problem. Response category 1 is scored 0. The x-axis represents median time in months after concussion at the three assessment points (baseline; end of intervention; 3-month follow-up). Abbreviations: EUC = enhanced usual care; GAIN = Get going After concussIoN; RPQ = Rivermead Post-concussion Symptoms Questionnaire.
Fig. A2
Fig. A2
BRIEF-A subscale and composite T-scores for participants ≥18 years at baseline (n = 84) and 3-month FU (n = 58). The x-axis represents T-scores. BRIEF-A raw scores were converted to T-scores based on US normative data. The reference line at T= 50 shows the US population mean. The dotted reference line at T = 65 indicates the recommended threshold for interpreting a score as elevated according to the manual (i.e. 1·5 SD above the population mean). Metacognition Index (MI) subscales: Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials. Behavioural Regulation Index (BRI) subscales: Inhibit, Shift, Emotional Control, and Self-Monitor. Global Executive Composite = MI + BRI. Abbriviations: BRIEF-A = Behaviour Rating Inventory of Executive Function - Adult Version; EUC = enhanced usual care; GAIN = "Get going After concussIoN".
Fig. A3
Fig. A3
Experience of Service Questionnaire modified (applied to patients allocated to GAIN+EUC, n = 54*). Item 1 – 10: from Experience of Service Questionnaire. Item 11 – 17 were added in order to evaluate the methods and materials. * Excluded from dataset (n= 3): Two patients allocated to GAIN (Get going After concussIoN) who never received the intervention and one patient who withdrew after 2 sessions and declined to receive any further questionnaires. Missing: n = 8.

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