Accepted Manuscript Work productivity loss after mild traumatic brain injury Noah D. Silverberg, PhD, William J. Panenka, MD, Grant L. Iverson, PhD PII:
S0003-9993(17)30492-6
DOI:
10.1016/j.apmr.2017.07.006
Reference:
YAPMR 56965
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 1 May 2017 Revised Date:
6 July 2017
Accepted Date: 7 July 2017
Please cite this article as: Silverberg ND, Panenka WJ, Iverson GL, Work productivity loss after mild traumatic brain injury, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/j.apmr.2017.07.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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*Corresponding author
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Disclosure of funding: This study was funded by a Specific Priorities Research Grant from
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WorkSafeBC (#RS2014-SP03). NDS receives salary support from a Clinician-Scientist Career
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Development Award from the Vancouver Coastal Health Research Institute.
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Work productivity loss after mild traumatic brain injury
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Noah D. Silverberg, PhD* Division of Physical Medicine & Rehabilitation, University of British Columbia; Rehabilitation Research Program, GF Strong Rehab Centre, Vancouver, Canada; Department of Physical Medicine and Rehabilitation, Harvard Medical School; Rehabilitation Research Program, 4255 Laurel St., Vancouver, BC, Canada, V5Z 2G9. Phone: 604-734-1313. Email:
[email protected]
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William J. Panenka, MD British Columbia Neuropsychiatry Program; Department of Psychiatry, University of British Columbia, Vancouver, Canada; 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T 2A1. Phone: 604-822-7314. Email:
[email protected]
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Grant L. Iverson, PhD Department of Physical Medicine and Rehabilitation, Harvard Medical School; Spaulding Rehabilitation Hospital; & Home Base, A Red Sox Foundation and Massachusetts General Hospital Program, Boston, USA; 79/96 13th Street, Charlestown, MA, USA, 02129. Phone: 617952-5000. Email:
[email protected]
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Running head: Work productivity loss after concussion
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Author Disclosure Statement: GLI has been reimbursed by the government, professional
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scientific bodies, and commercial organizations for discussing or presenting research relating to
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MTBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has
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a clinical practice in forensic neuropsychology involving individuals who have sustained mild
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TBIs. He has received honorariums for serving on research panels that provide scientific peer
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review of programs. He is a co-investigator, collaborator, or consultant on grants relating to mild
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TBI funded by several organizations. NDS has a private practice in neuropsychology that
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includes consultation roles with professional sport organizations and disability insurance
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providers. WP has a clinical practice in forensic neuropsychiatry involving individuals who have
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sustained TBIs.
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Acknowledgements: The authors wish to thank research assistants Mary Ellen Johnson and
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Sabrina Khan as well as the clinical staff at our recruitment sites, including Kelsey Davies,
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Jennifer Loffree, Grace Boutilier, and Trish Mahoney (GF Strong Rehab Centre), Deanna Yells,
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Heather MacNeil, and Rod Macdonald (Fraser Health Concussion Clinic), Denise Silva and
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Lesley Norris (Back in Motion), and Karilyn Lao, Wayne Tang, and Cyrus Huang (LifeMark).
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The authors additionally wish to thank Dr. Joukje van der Naalt (University of Groningen) for
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raising the hypothesis that participants who recently returned to work at the time of the follow-up
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assessment may have been experiencing an activity-related symptom exacerbation, when
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preliminary data from the present study were presented at the 2017 World Congress of the
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International Brain Injury Association in New Orleans, USA.
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Work productivity loss after mild traumatic brain injury
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Abstract
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Objective: To examine the completeness of return to work (RTW) and the degree of
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productivity loss in individuals who do achieve a complete RTW after mild traumatic brain
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injury (MTBI).
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Design: Multi-site prospective cohort.
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Setting: Outpatient concussion clinics.
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Participants: Seventy-nine patients (M=41.5 years old, 55.7% female) who sustained an MTBI
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and were employed at the time of the injury. Participants were enrolled at their first clinic visit
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and assessed by telephone 6-8 months post-injury.
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Intervention: None.
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Measures: Structured interview of RTW status, British Columbia Postconcussion Symptom
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Inventory (BC-PSI), Lam Employment Absence and Productivity Scale (LEAPS), MINI
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Neuropsychiatric Interview, brief pain questionnaire. Participants who endorsed symptoms from
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three or more categories with at least moderate severity on the BC-PSI were considered to meet
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International Classification of Diseases-10 criteria for postconcussional syndrome. RTW status
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was classified as complete if participants returned to their pre-injury job with the same hours and
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responsibilities or to a new job that was at least as demanding.
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Results: Of the 46 (58.2%) patients who achieved a RTW, 33 (71.7%) had a complete RTW.
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Participants with complete RTW had high rates of postconcussional syndrome (44.5%) and
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comorbid depression (18.2%), anxiety disorder (24.2%), and bodily pain (30.3%). They also
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reported productivity loss on the LEAPS, such as “getting less work done” (60.6%) and “making
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more mistakes” (42.4%). In a regression model, productivity loss was predicted by the presence
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of postconcussional syndrome and a comorbid psychiatric condition, but not bodily pain.
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Conclusion: Even in patients who RTW after MTBI, detailed assessment revealed
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underemployment and productivity loss associated with residual symptoms and psychiatric
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complications.
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Key Words: Craniocerebral Trauma; Post-Concussion Symptoms; Presenteeism; Occupational
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Health; Return to Work
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Introduction In most observational studies, 60% to 90% of patients return to work (RTW) within six months after a mild traumatic brain injury (MTBI)(1–14). Although encouraging, there is
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evidence that some of these patients do not return to their pre-injury level of employment. For
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example, in a cohort of patients who returned to work after being admitted to hospital with
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MTBI, only 28.5% (6 of 21 patients) resumed their pre-injury level of employment, with the
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remainder returning to modified duties or reduced hours(15). Larger inception cohort studies
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have reported more favorable rates. Of patients who RTW in some capacity after MTBI, 70-80%
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did so completely(12,14). Taken together, these data suggest caution about treating RTW as a
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dichotomous variable and using it as a proxy for functional outcome in MTBI research.
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RTW rates may also overestimate recovery after MTBI if some patients who RTW have
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residual symptoms that impact their productivity. There is a large literature on productivity loss
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(or “presenteeism”) due to various health problems(16). The costs of productivity loss outweigh
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that of absenteeism and disability leave(16). Conditions such as depression and chronic pain are
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well-known to reduce work output and interpersonal effectiveness at work(16). Less is known
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about productivity loss after MTBI. In a structured interview of patients with mild to moderate
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TBI who achieved a RTW (N=160), half (46%) reported ongoing difficulties with remembering
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or concentrating at work(12). In another study that included patients with TBI of all severities,
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one third of patients who returned to their pre-injury level of employment reported residual
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cognitive (e.g., memory, thinking speed, and concentration) and/or behavioral problems (e.g.,
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irritability, apathy)(14). Of note, incomplete RTW and productivity loss may be associated with
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both MTBI and factors that are peripherally related (e.g., comorbid orthopaedic injury) or
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unrelated to MTBI (12–14).
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The present study aimed to better characterize the completeness of RTW after MTBI and
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the degree of productivity loss in individuals who do achieve a complete RTW. We describe
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vocational outcomes in a cohort of clinic-referred patients who were employed prior to their
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MTBI. We hypothesized that a proportion of those who RTW will do so incompletely, i.e., with
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modified duties or hours, accommodations, or to a less demanding job. We further hypothesized
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that some patients who achieved a complete RTW would report productivity loss associated with
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residual postconcussional symptoms and comorbid conditions such as depression and bodily
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pain. The present study findings should add to our understanding of the vocational impact of
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MTBI.
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Methods
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Participants were recruited from consecutive referrals to four outpatient concussion specialty clinics in the greater Vancouver area from March 2015 to February 2017. Two of these
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clinics operate in the public health sector, for people with non-workplace injuries, and two are
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private clinics that can be accessed by Workers’ Compensation claimants. The eligibility criteria
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were: (i) age 18 to 65, (ii) sustained an MTBI by the World Health Organization Neurotrauma
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Task Force operational definition(17) within the past six months, (iii) fluent in English, and (iv)
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employed prior to injury. The present study received approval from the University of British
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Columbia Behavioural Research Ethics Board, the Vancouver Coastal Health Research Institute,
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and the Fraser Health Research Institute.
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Participants were evaluated upon presentation to clinic (M=11.7 weeks post-injury,
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SD=6.4) and again 4-5 months later (M=31.7 weeks post-injury, SD=6.1), after completing any
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rehabilitation. Figure 1 displays participants flow through the study. Demographic and injury
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characteristics were obtained by structured interview in an initial in-person assessment. In a
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telephone follow-up assessment, participants were interviewed about their RTW status and
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completed self-report measures. Figure 2 shows the questions participants were asked about their
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RTW status and how participants were classified on the basis of these questions into complete,
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partial, and no RTW groups. The follow-up assessment also included the measures listed below.
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British Columbia Postconcussion Symptom Inventory (BC-PSI)(18), a rating scale for physical, cognitive, and emotional symptoms designed to map on to the International
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Classification of Diseases-10 criteria for Postconcussional Syndrome (PCS). Frequency and
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severity ratings are combined into item scores. Participants met diagnostic criteria for PCS if
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they endorsed symptoms as moderate severity or worse (i.e., item scores of 3 or higher) in at
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least three categories, as defined by the International Classification of Diseases-10. A total score
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on BC-PSI was also created by summing the item scores.
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Lam Employment Absence and Productivity Scale (LEAPS)(19), a standardized measure of absenteeism and presenteeism with adequate psychometric properties(20), originally
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developed for Major Depressive Disorder. On the LEAPS, respondents are asked how much
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work they missed over the past two weeks due to feeling unwell and to rate how often they
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experienced troublesome symptoms and productivity problems, when at work. Higher ratings
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indicate more problems. A total score is calculated by summing the item ratings (4a-4g). The
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factor-analytic derived productivity subscale (LEAPS-P) is calculated by summing items 4d-4f
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and represents a more psychometrically pure measure of productivity loss(19).
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MINI Neuropsychiatric Interview(21,22). The MINI is a brief structured interview for
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identifying psychiatric disorders. It has been validated against comprehensive diagnostic
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evaluations(21,22). There have been several iterations of the MINI. The mood, anxiety, and
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substance use disorder modules from Version 6.0, based on the Diagnostic and Statistical
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Manual of Mental Disorders (Fourth Edition), were used in the present study.
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Bodily pain. In order to better capture chronic bodily pain associated with the index injury (vs. pain from pre-existing or unrelated conditions), we classified participants as having a
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comorbid pain condition if they reported (1) requiring urgent medical attention for non-head
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injuries associated with the index MTBI, and (2) moderate or worse current pain (i.e., item rating
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of 2 or 3 on Likert scale that ranged from 0 to 3) in a body region other than head when assessed
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at follow-up.
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Pairwise group differences were examined with t-tests for continuous variables and chi-
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squared (χ2) tests for proportions. Contrasts below a p value of 0.05 were considered significant.
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We did not correct for multiple comparisons because most statistical tests evaluated a different
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hypothesis, and this is exploratory-phase research(23). Linear regression was performed within
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the complete RTW group. Three dichotomous predictors were simultaneously entered into the
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model predicting LEAPS: PCS, any psychiatric disorder (depression, an anxiety disorder, or
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substance use disorder), and bodily pain. We initially performed these analyses with the LEAPS
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total score, and then performed sensitivity analyses with the LEAPS-P, a more unidimensional
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measure of productivity loss.
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Results
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Participants who were lost to follow-up (N=13) were similar to retained participants
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(N=79) with respect to age (M=38.2 vs 41.5 years old; t(90)=.926, p=.357), sex (46.2% vs.
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55.7% female; χ2 =.410, p=.522), education (52.2% vs. 38.5% with a post-secondary degree; χ2
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=.966, p=.326) ethnicity (61.5% vs. 75.9% Caucasian; χ2 =.1.20, p=.273). Of the 79 participants
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assessed at follow-up, 46 (58.2%) achieved a RTW, with 33 (71.7%) of those having a complete
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RTW and the remainder classified as having a partial RTW due to ongoing modified duties,
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hours, or accommodation, or because they returned to a different, less demanding job. The
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demographic and clinical profiles of the complete, partial, and no RTW groups are shown in
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Table 1. No major differences in RTW rates based on age, sex, education, ethnicity, or
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occupational status were apparent, though some of these cell sizes were very small, preventing
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robust statistical testing. As expected, participants who were not working at the follow-up
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assessment generally had highest group proportions of PCS, psychiatric comorbidity, and bodily
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pain. A similar proportion of participants with workplace MTBI (N=37) vs non-workplace MTBI
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(N=42) had complete RTW (43.2% vs. 40.5%), PCS (58.3% vs 69.4%), any psychiatric
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comorbidity (50.0% vs. 50.0%), and bodily pain (37.1% vs. 35.7%). For the total sample, those
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who met criteria for depression, an anxiety disorder, or who had bodily pain reported more
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productivity loss on the LEAPS total score (n=23, M=9.09, SD=5.14) than those who did not
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have any of these comorbidities (n=23, M=4.30, SD=3.43; t(44)=3.71, p=.001, Cohen’s d=1.10).
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Similar differences were apparent on the LEAPS-P, M=3.17 (SD=2.35) vs. M=1.30 (SD=1.72),
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t(44)=3.08, p=.004, Cohen’s d=0.91.
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Of note are the high (absolute) proportions of PCS, psychiatric comorbidity, and bodily
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pain in the complete RTW – a group of patients who reported fully returning to their pre-injury
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level of employment. The analyses that follow focus on this complete RTW group. Participants
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with complete RTW reported some missed work over the past two weeks on the LEAPS, as
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follows: 63.6% missed no work, 6.1% missed less than one full shift, and 21.2% missed 1-2
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shifts, and 9.1% missed more than 2 shifts. Participants in the complete RTW also reported
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productivity loss on the LEAPS. The most frequently endorsed items were “getting less work
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done” (n=20; 60.6%), “making more mistakes” (n=12; 42.4%), “having interpersonal
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difficulties” (n=12; 36.4%), and “doing poorer quality work” (n=9; 27.3%). The LEAPS total
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score [r(33)=.74, p<.001] and LEAPS-P [r(33)=.71, p<.001] correlated strongly with post-
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concussion symptom severity (BC-PSI total score). Participants with workplace MTBI (N=16)
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and non-workplace MTBI (N=17) reported a similar degree of productivity loss [LEAPS total
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score M=5.13 vs. 7.29, t(31)=1.14, p=0.265; LEAPS-P M=1.38 vs. 2.65, t(31)=1.53, p=0.137].
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Participants in the complete RTW group returned to work at a median of 14.5 weeks (interquartile range = 8-24 weeks) before the follow-up assessment. We considered the
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possibility that individuals who had recently returned to work may have exacerbated post-
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concussion symptoms related to physical and/or cognitive exertion*, whereas those who had
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been back at work for longer may have built up their activity tolerance and/or experienced
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further recovery. The Pearson correlation between the RTW-assessment interval and the BC-PSI
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total score was in the expected direction, but did not reach significance, r(33)=-.233, p=.214.
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Time since RTW was also not significantly related to the LEAPS total score [r(33)=.148,
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p=.435] or LEAPS-P [r(33)=.116, p=.528]. In summary, the timing of RTW did not appear to
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strongly influence the primary outcomes of interest in this study.
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In a linear regression analysis, the LEAPS total score was the dependent variable. Three
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dichotomous predictors, PCS, any psychiatric diagnosis, and bodily pain, were entered
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simultaneously. The overall model was significant, F(3,28)=18.2 p<.001, explaining two thirds
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of the variance in productivity loss (R2=0.669). There was no problematic multicollinearity
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(Variance Inflation Factors all < 2.0 and Conditional Indices all < 10). The presence/absence of
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PCS (β=.547, t=4.55, p<.001) and any psychiatric comorbidity (β=.437, t=3.70, p=.001) each
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uniquely predicted work impairment, with a similar magnitude. Bodily pain was not a significant
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predictor in the multivariable model (β=.038, t=.329, p=.745). The same regression analysis with
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LEAPS-P as the dependent variable produced similar results, F(3,28)=12.24 p<.001, R2=.576,
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β=.439 for PCS, β=.471 for psychiatric comorbidity, and β=.053 for bodily pain.
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Discussion By conducting a detailed assessment of RTW status, we discovered underemployment
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and productivity loss in patients who would normally be considered to have a “good” outcome
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because they resumed working after MTBI. Specifically, 1 in 4 patients who had returned to
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work were still on modified duties, working reduced hours, or receiving accommodations, or
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took a different, less demanding job. This rate of incomplete RTW is similar to that found in
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prior studies that recruited from Emergency Departments(12,14). The present study also
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demonstrated residual problems in the group of patients with complete RTW, i.e., those who
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returned to their pre-injury jobs, with the same hours and responsibilities. About half reported
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multiple cognitive, physical, and emotional symptoms of at least moderate severity, sufficient to
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meet International Classification of Diseases-10 criteria for PCS. Rates of comorbid psychiatric
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disorders and bodily pain were also high in this group. Participants with complete RTW reported
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productivity loss. When considered together in a multivariable regression model, having PCS or
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a psychiatric condition each significantly predicted productivity loss. In summary, the most
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important findings from this study were that RTW after MTBI is sometimes incomplete and that
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even when complete, there can be productivity loss associated with residual symptoms and
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psychiatric comorbidity.
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Absenteeism and productivity loss could threaten the long-term stability of
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employment(24). It is noteworthy that prior unsuccessful RTW attempts were common (20-30%)
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in the complete and partial RTW groups (Table 1). This may suggest that a subset of workers are
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in fragile employment situations, at high risk for another failed RTW. However, considering all
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kinds of injuries (not only MTBI), approximately 20% of injured workers take multiple RTW
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attempts before achieving a durable RTW, while another 10% fail despite multiple attempts(25).
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So, multiple attempts is not necessarily an indicator for eventual RTW failure. Further
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longitudinal research is needed to document the durability of RTW after MTBI and identify
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factors associated with durable vs. unstable RTW.
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The overall rate of RTW in this sample (58.2% by about six months post-injury) was somewhat lower than in most prior studies recruited from consecutive Emergency Department
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visits or hospital admissions(1–4,6–14). This is not surprising because we recruited from
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outpatient concussion clinics, where patients are referred (most often by a family physician or
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disability claim manager) or self-refer because of an atypically slow recovery. Our sampling
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method may also explain the relatively high rates of psychiatric comorbidity compared to
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unselected MTBI samples(26,27).
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Study Limitations
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As mentioned, our sample was probably representative of patients who present to
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outpatient specialty clinics for MTBI care, but not of the broader MTBI population. Although the
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drop-out rate was similar or lower than most longitudinal MTBI studies, attrition bias could have
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influenced the present findings. There is some prior evidence that participants with favorable
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recoveries tend to drop out of research at higher rates(28). RTW status and productivity loss
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were both assessed by patient self-report, and could have been distorted by response bias.
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Symptom exaggeration may have been less likely because our participants were assessed in a
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research context(29) and the focus was on individuals who fully returned to their pre-injury
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employment, most (85%) of whom perceived to be no longer eligible for injury benefits or
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compensation. Participants in this study were followed to an average of 6-8 months post injury.
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We do not know if the residual symptoms or work modifications/accommodations documented
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at this time point are permanent. Some may have achieved a fuller RTW with a complete
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restoration in productivity if observed for a longer period. There may be important differences
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between occupational categories with respect to rates of RTW and productivity loss after MTBI.
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We did not have sufficient sample size to investigate this possibility. The MINI Neuropsychiatric
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Interview was administered by a trained research assistant, under the supervision of a
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psychologist. Diagnostic interviews conducted by a mental health professional may have been
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more accurate. Another limitation is that the present study did not include control groups of
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healthy workers or workers who sustained non-brain injuries. To some degree, the concussion-
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like symptoms and work productivity problems that participants reported may be pre-existing or
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caused by non-brain injury factors (e.g., life stress). Future studies should include injured
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workers presenting to specialty clinics for bodily injuries not involving the head.
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Conclusions
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The present study findings caution against using a binary RTW variable as an endpoint in MTBI research. Individuals who RTW after MTBI sometimes do so incompletely or have
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residual symptoms and productivity loss. More granular functional outcome measures could
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better characterize recovery from MTBI and improve prognostic modeling. Clinicians who
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support patients with MTBI to RTW should be aware that incomplete symptom resolution and
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RTW can be compatible. RTW may be better characterized as a stage of recovery rather than an
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outcome(30). Temporary accommodations likely facilitate a successful RTW(31,32). The
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economic and psychological benefits of RTW(33) must be weighed against the risk of premature,
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unsuccessful RTW. The present study also suggests that some workers may require ongoing
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clinical support after initiating a RTW to effectively manage their residual symptoms and
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maintain employment. Telephone coaching on symptom management may be a feasible and
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cost-effective strategy to meet these needs(34,35). The present findings also suggest that
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screening for psychiatric complications should continue past the point of RTW.
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Table 1. Demographic and clinical characteristics of the sample, stratified by return to work status. Complete
Partial RTW
RTW
(n=13)
(n=79)
(n=33)
(n=33) 41.5 (12.0)
39.6 (11.3)
Sex, n females (%)
44 (55.7%)
17 (51.5%)
M AN U
Less than high school diploma
41.8 (13.2)
SC
Age, M (SD)
Education, n (%)
No RTW
RI PT
Full Sample
43.4 (12.4)
6 (46.2%)
21 (63.6%)
6 (7.6%)
3 (9.1%)
1 (7.7%)
2 (6.1%)
18 (22.8%)
6 (18.2%)
3 (23.1%)
9 (27.3%)
13 (16.5%)
8 (24.2%)
3 (23.1%)
2 (6.1%)
11 (13.9%)
2 (6.1%)
1 (7.7%)
8 (24.2%)
24 (30.3%)
12 (36.4%)
2 (15.4%)
10 (30.3%)
7 (8.9%)
2 (6.1%)
3 (23.1%)
2 (6.1%)
Manual labor
17 (21.5%)
9 (27.3%)
5 (38.5%)
3 (9.1%)
Skilled craft or trade
11 (13.9%)
3 (9.1%)
2 (15.4%)
6 (18.2%)
Sales and service
8 (10.1%)
2 (6.1%)
1 (7.7%)
5 (15.5%)
Clerical
5 (6.3%)
1 (3.0%)
1 (7.7%)
3 (9.1%)
High school diploma
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Some college, no degree College diploma
EP
Bachelor’s degree Post-graduate degree
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Occupational category, n (%)
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Management/professional
18 (22.8%)
9 (27.3%)
2 (15.4%)
7 (21.2%)
Other
20 (25.3%)
9 (27.3%)
2 (15.4%)
9 (27.3%)
Caucasian
60 (75.9%)
22 (66.7%)
Asian-Canadian
11 (13.9%)
6 (18.2%)
First Nations
5 (6.3%)
3 (9.1%)
1 (7.7%)
1 (3.0%)
Other
3 (3.8%)
2 (6.1%)
0 (0%)
1 (3.0%)
disability benefits, n (%) Hired lawyer for injury compensation
Prior unsuccessful attempt(s) to RTW, n
EP
yes (%)
International Classification of Diseases-
27 (81.8%)
2 (15.4%)
3 (9.1%)
SC
10 (76.9%)
25 (31.7%)
2 (15.4%)
4 (30.8%)
19 (57.6%)
23 (29.1%)
7 (21.2%)
4 (30.8%)
12 (36.4%)
15 (19.0%)
10 (30.3%)
3 (23.1%)
2 (6.1%)
46 (58.2%)
16 (44.5%)
8 (61.5%)
22 (66.7%)
20.0 (13.4)
15.0 (13.2)
19.5 (10.8)
25.0 (13.0)
6.7 (4.9)
6.2 (5.5)
7.8 (3.0)
--
TE D
claim, n (%)
M AN U
Seeking or receiving administrative
RI PT
Ethnicity, n (%)
AC C
10 criteria for Postconcussional Syndrome, n (%)
British Columbia Postconcussion Symptom Inventory total score, M (SD) Lam Employment Absence and Productivity Scale total score, M (SD)
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Lam Employment Absence and
2.2 (2.2)
2.0 (2.4)
2.8 (1.6)
--
23 (29.1%)
6 (18.2%)
2 (15.4%)
15 (45.5%)
28 (35.4%)
8 (24.2%)
6 (46.2%)
14 (42.4%)
7 (8.9%)
1 (3.0%)
Productivity Scale productivity subscale
MINI diagnosis of Major Depressive
MINI diagnosis of any anxiety disorder,
MINI diagnosis of substance use disorder, n (%)
29 (36.7%)
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EP
TE D
Bodily injury with current pain, n (%)
M AN U
n (%)
SC
Disorder, n (%)
RI PT
score, M (SD)
10 (30.3%)
2 (15.4%)
4 (12.1%)
2 (15.4%)
17 (51.5%)
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M AN U
SC
RI PT
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TE D
M AN U
SC
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