Table 3 Secondary outcomes

Cognitive Testing

Executive function, visual attention, task switching

The Oral Trail Making Test (O-TMT) (versions A and B) will be used to evaluate executive function, visual attention, and task switching in participants. During O-TMT A, participants will be asked to count out loud from 1 to 25 and is primarily a measure of processing speed and simple attention. During O-TMT B, participants will be asked to alternate saying numbers and letters (1-A, 2-B, etc.) and is a measure of mental flexibility. Time to completion as well as total errors are recorded [34, 35]. The use of time and error rate led to slightly improved classification rates for cognitive impairments compared to either alone [36].

Verbal learning and memory

The Hopkins Verbal Learning Test-Revised (HVLT-R) will be used to evaluate verbal learning and memory capabilities in participants [37]. The HVLT consists of a 12-item word list, composed of four words from each of three semantic categories. The list is read to participants at a rate of approximately 2 words per second. Participants are then asked to free recall the list of words. This is repeated for 3 trials. After the third trial and a 20–25-min delay (with no forewarning), participants will again be asked to free recall the 12 words and then will be read 24 words and asked to say “yes” after each word that appeared on the recall list (12 targets) and “no” after each word that did not (12 distractors) [38]. The HVLT is available in 6 forms to reduce test-retest learning effects, takes no more than 10 min to administer and is shown to be well tolerated by participants [37].

Attention, Working memory

The Digit Span subset, a component of the Working Memory Index of the Weschler’s Adult Intelligence Scale - 4th Edition (WAIS-IV), will be used to assess attention and working memory [39]. Participants will be read a series of numbers and then asked to recall the numbers to the examiner in order (forward span), in reverse order (backward span), and in sequence (sequence span). Participants will complete spans of increasing length, with two trials at each length, until an error is made on both trials of a given length. Digit Span has shown good internal consistency and test-retest reliability across age groups [39, 40].

Verbal fluency

The Phonemic and Semantic Verbal Fluency (or Controlled Oral Word Association Test [COWAT]) test will be used to assess verbal fluency. Participants will be given 1 min to produce as many unique words as possible: (1) within a semantic category (category fluency for Animals); and (2) starting with a given letter (letter fluency for letters F, A, and S). The COWAT has been shown to have sensitivity to brain lesions and conditions with impaired cognition (e.g., traumatic brain injury). Population norms are available for the COWAT for a broad age (16–95) and education (0–21 years) range [41, 42].

PHQ-9

Depression

A 9-item questionnaire that assesses the severity of depression symptoms experienced within the last 2 weeks. Participants are asked to rate each symptom of depression on a Likert scale from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0 (minimal depression) to 27 (severe depression). The PHQ-9 has strong methodological properties with an internal consistency of 0.89 and strong test-retest reliability [43].

GAD-7

Anxiety

A 7-item questionnaire that assesses the severity of anxiety symptoms experienced within the last 2 weeks. The initial validation study, conducted by Spitzer et al. (2006), demonstrated high internal consistency (α=0.92) and test-retest reliability (intraclass correlation = 0.83) [44].

PSQI

Sleep

The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality in the previous month and takes 5–10 min to complete. It has been translated into over 50 languages. Using a threshold score of greater than 5, the PSQI showed a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p < 0.001) in distinguishing “good” and “poor” sleepers [45].

PSTD Checklist 5 (PCL-5)

Post-traumatic stress disorder

A 20-item self-report measure that assesses the presence and severity of PTSD symptoms, corresponding with DSM-5 criteria for PTSD. The PTSD Checklist 5 (PCL-5) scores exhibit strong internal consistency (α = .94), test-retest reliability (r = .82), and convergent (rs = .74 to .85) and discriminant (rs = .31 to .60) validity [46].

EQ-5D-5L

Quality of life

This is a 5-item questionnaire that assesses health-related quality of life, including mobility, self-care, ability to participate in one’s usual activities, pain or discomfort, and anxiety or depression and a visual analog scale (VAS) which asks participants to evaluate their overall health on a scale from 0 to 100. It is available in multiple languages, and there are standardized scores for patient populations in different settings. The EQ-5D-5L is able to define a unique health state based on the responses to each of the five dimensions of health described above [47].

AUDIT

Alcohol use

The AUDIT questionnaire is designed to assess alcohol consumption, drinking behavior, adverse reactions, and alcohol-related problems. Among those who were known to misuse alcohol, the AUDIT successfully detected an alcohol use disorder 99% of the time [48].

ASSIST

Alcohol and substance use

The ASSIST is a brief interview collecting information regarding use of tobacco, alcohol, cannabis, cocaine, amphetamine type stimulants, sedatives, hallucinogens, inhalants, opioids, and other drugs. Internal Consistency (Chronbach’s alpha) was over 0.80 for the majority of domains and good concurrent validity [49, 50].

FSS

Fatigue

The Fatigue Severity Scale (FSS) is a 9-item self-report that measures the severity and functional impact of fatigue. The scale demonstrated good internal consistency (Cronbach’s α 0.88), as well good test-retest reliability and sensitivity to clinical change [51].

Fatigue Numeric Rating Scale

Fatigue

A single-item patient-reported outcome, scored on a scale of 0–10, with good test-retest reliability (ICC=0.79, p < 0.008) and sensitivity to change [52].

Pain Numeric Rating Scale

Pain

The Pain Numeric Rating Scale will be used to assess pain intensity using a 0–10 ranking scale, where 0 represents “no pain” and 10 “unbearable pain.” The scale shows good test-retest reliability (ICC=0.72 for single item), and sensitivity [53]. Pain may be categorized using Mild (scores ≤5), Moderate (scores 6–7), or Severe (scores ≥8) [54].

MRC Dyspnoea Scale

Breathlessness

A 5-item self-report scale that evaluates statements of perceived breathlessness. The scale has good correlation to level of disability due to breathlessness [55].

WEMWBS

Wellbeing

The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) (short version) is a 7-item scale which measures multiple aspects of mental wellbeing [56]. It has been validated in general population samples and in English and French [57], and is sensitive to change [58].