Participants and procedure

Participants were 71 patients presenting to the emergency department of the John Radcliffe Hospital (Oxford, UK) (Figure 1): 34 were men and 37 were women, and the mean age was 39.66 years (s.d. 16.32). Inclusion criteria were: age ⩾18 years; experienced/witnessed a motor vehicle accident (as a driver, passenger, motorcyclist or pedestrian); met Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV) PTSD criterion A1 for a traumatic event ('experienced, witnessed or was confronted with an event or events that involved actual or threatened death or serious injury'); seen in emergency department within 6 h of leaving scene of the accident; reported memory of the accident; fluent in written and spoken English; alert and orientated, Glasgow Coma Scale37 score=15; and sufficient physical mobility to play a computer game on the intervention platform (Nintendo DS) at the point of taking informed consent. Exclusion criteria were loss of consciousness for >5 min, reported history of severe mental illness, current intoxication, substance abuse or neurological condition, or currently suicidal. The study was approved by the local National Research Ethics Service Research Ethics Committee (Oxford C: 12/SC/0485).

Figure 1 CONSORT participant flow diagram for the trial. PowerPoint slide Full size image

Potential participants were identified by emergency department staff. Eligibility was assessed by a clinical psychologist (LI) using information from medical records and face-to-face interview. After receiving a description of the study, all participants provided written informed consent before completing baseline measures. Participants were then randomly allocated in a 1:1 ratio to two parallel treatment conditions using a web-based randomization system, provided by the Oxford Cognitive Health and Neurosciences Clinical Trials Unit and verified by independent statisticians. Randomization was used to balance groups on known and unknown baseline predictors of outcome,38 and carried out using minimization39 based on gender, age and perceived life threat to self, with an additional random component to ensure allocations remained unpredictable. The randomization system was accessed by the researcher (LI) from a separate office after baseline measures had been completed. Participants were not informed as to condition allocation. The researcher delivering the procedures (LI) was not blind to participant allocation, as the need to provide verbal instructions precluded such blinding.

Outcome assessment was scheduled for 1 week and 1 month after the accident. After 1-month follow-up, participants were contacted by telephone and debriefed. They were offered a £30 GBP ($45 USD) store voucher to compensate them for their time. Recruitment occurred between March 2014 and January 2015. The last follow-up assessment was completed in February 2015. The trial ended once the planned sample size had been achieved.

Assessments

Traumatic event and emergency department treatment characteristics

Details of participants’ traumatic event, treatment in the emergency department and previous emergency department attendances were collected from medical records. Severity of physical injury, indicated by the Injury Severity Score (range 0–75), was rated using the Abbreviated Injury Scale.40 Agreement for injury codings between raters (LI and a research nurse) was 100%. Participants rated perceived life threat during the accident: 'to what extent did you feel your life was in danger?' and 'to what extent did you feel that someone else’s life was in danger?' from 0 (not at all) to 10 (extremely).41 Dissociative symptoms were assessed with the Peritraumatic Dissociative Experiences Questionnaire-Self Report.42 Emotional responses were assessed with the Peritraumatic Distress Inventory.43 Participants reported experience of prior psychological trauma, current and past mental illness, and family history of mental illness.

Primary outcome

The total number of intrusive memories in the week after the traumatic event was assessed using a daily pen-and-paper diary (adapted from refs 15, 29, 35). Participants recorded the occurrence of intrusive memories in everyday life by ticking a box for the day and time period (morning/afternoon/evening) when the intrusive memory occurred, or marked 'zero' if they experienced none. Intrusive memories were described as: 'image-based memories of the accident that pop into your mind without warning. They often take the form of visual pictures in your mind’s eye, for example, like a snapshot image or a film clip. They can also include other senses, for example, sounds and smells'. Participants were not to record memories recalled deliberately or general verbal thoughts. For examples of intrusive memories see Supplementary Table 2. The diary started on the day of the accident ('Day 1') and was completed for seven days. Daily reminders to complete the diary were sent via SMS. Upon completion, participants rated 'how accurately do you think you completed the diary?' from 0 (not at all) to 10 (extremely). Participants returned the diary by post. The number of intrusive memories was selected for several reasons: it allows comparison with preclinical work; was readily understood by traumatized patients without the need for explanation from an expert; and is directly relevant to the clinical goal of reducing the number of times the memory intruded (not just reducing its intensity).

Secondary outcomes

Post-trauma distress was assessed using the Impact of Event Scale—Revised,40, 45 which has subscales for intrusion, avoidance and hyperarousal symptoms. PTSD symptom severity was assessed with the Post-traumatic Diagnostic Scale (PDS; Foa46). Anxiety and depression symptoms were assessed with the Hospital Anxiety and Depression Scale.47 To minimize assessor bias and participant burden, measures were completed remotely (online using the secure web-based software 'Qualtrics'48 or by post).

Participant feedback

A 13-item feedback questionnaire assessed participants’ experience of the study. Items included ratings of how easy, helpful and distressing/burdensome participants found playing Tetris on a scale from 1 (not at all) to 9 (extremely), expectancy ratings for their condition on number of intrusive memories on a 21-point scale from −10 (extreme decrease), 0 (no effect) to +10 (extreme increase)35 and open questions.

Treatment conditions

Participants in both treatment conditions received usual care in the emergency department (e.g. assessments and medical treatment). The condition-specific procedures below were delivered around usual care by a clinical psychologist (LI). Both condition-specific procedures were standardized and structured.

Intervention

The intervention procedure involved two key components: a reminder cue for the traumatic event followed by playing the computer game Tetris.29 For the memory reminder cue, participants were asked to think back to the accident and briefly tell the researcher the worst moments that came to mind.49 Following instructions and practice, participants played Tetris on a Nintendo DS XL. Participants were required to undertake minimum Tetris game play for at least one uninterrupted period of 10 min and for ~20 min in total.

Control

In the control procedure participants filled in a simple activity log to note down each activity they had already engaged in during their time in the emergency department. They wrote brief entries in a list in a column (e.g., reading, talking, receiving treatment, crossword, texting) and recorded each activity’s duration (in minutes) in a second column. Following instructions of how to complete the log, participants completed it using pen-and-paper on a clipboard for ~20 min (a similar duration to the intervention condition).

Time spent playing Tetris and filling the activity log was equivalent; and total time spent in the emergency department, during which other activities were unrestricted, was equivalent in the two conditions (Supplementary Information).

Data analysis

Power analysis

Using a conservative estimated effect size of Cohen’s d=0.7, based on a previous laboratory study,29 a total sample size of n=66 was required to provide 80% power at α=0.05, two-tailed. Recruitment of at least 70 participants was planned to allow for attrition.

Main efficacy analyses

Analyses were intention-to-treat, including all randomized participants. Missing values were estimated using multiple imputation. Five data sets were generated for each missing value at 1 week follow-up, and 10 data sets for each missing value at 1-month follow-up, in line with the recommendation that the number of data sets approximates the percentage of missing data.50 Treatment group, age, gender and perceived life threat to self were included as auxiliary variables.51 Estimates were pooled in line with guidelines for multiple imputation.52 As all between-group comparisons in continuous outcomes at 1 week and 1 month were planned a priori, differences were tested using two-tailed t-tests at α=0.05 (ref 53, p 372). Cohen’s d effect sizes were calculated as t[Sqrt(1/n1+1/n2)], and 95% confidence intervals for the effect size were calculated using ESCI software.54 Percentage of participants with a symptom profile on the PDS consistent with a DSM-IV diagnosis of PTSD was compared between conditions using logistic regression (2 × 2 χ2 test) at α=0.05, two-tailed. Efficacy analyses were conducted in SPSS version 2255 by the first author and verified by a statistician (PCW) blind to condition. Before analysis, 100% of raw data for the primary efficacy analysis, and a randomly selected 10% of raw data for the secondary efficacy analyses, were checked for accuracy by a researcher not involved in data collection and blind to condition. Analyses were also conducted on a 'per-protocol' population (Supplementary Table 3).

Exploratory analyses

To investigate the time course of intrusive memories reported in the daily diary over the first seven days after the accident, frequency scattergraphs showing the distribution of the number of intrusive memories on each day per condition were plotted. A nonlinear time-series analysis was used to produce a nonparametric line of best fit, summarizing the distribution of the number of intrusive memories on each day, smoothed from day to day over the 7-day period, by accounting for the number of intrusive memories at nearby time points (autocorrelation). This was achieved by fitting counts of the number of intrusive memories for each participant (Y) through time (t) with a generalized additive model:56

where u is a random variable of time and s(t, 4) is the smoother with four effective degrees of freedom (as in James et al.35). Expected Poisson distributions at day 2 and day 7 were generated. Time-series analyses were undertaken in R using data provided by participants who returned the diary (n=67).

Code availability

The computer code used to generate the results can be accessed via Open Science Framework at https://osf.io/e4hc7.