http://informahealthcare.com/bij ISSN: 0269-9052 (print), 1362-301X (electronic) Brain Inj, 2014; 28(10): 1248–1256 ! 2014 Informa UK Ltd. DOI: 10.3109/02699052.2014.916420

ORIGINAL ARTICLE

Sustained outcomes following mild traumatic brain injury: Results of a five-emergency department longitudinal study Jess F. Kraus1, Paul Hsu2, Kathryn Schafer3, & A. A. Afifi4 1

Department of Epidemiology, UCLA, San Marcos, CA, USA, 2Department of Epidemiology, UCLA, Los Angeles, CA, USA, 3Scripps Memorial Hospital Trauma Service, La Jolla, CA, USA, and 4Department of Biostatistics, UCLA, CA, USA

Abstract

Keywords

Objective: To report on the occurrence of sustained outcomes including post-concussion symptoms, health services used and indicators of social disruption following a mild traumatic brain injury (MTBI). Research design: A dual cohort comparing MTBI Emergency Department (ED) patients and a comparison group of non-head injured ED patients. Methods and procedures: The outcomes measures employed were the Rivermead PostConcussion Symptoms Questionnaire (RPQ) and indicators of health services used and social disruption all recorded at the ED and at 3 and 6 months post-ED discharge. ‘Sustained’ meant a positive response to these measures at 3 and 6 months. Main outcomes and results: Reasonable follow-up success was achieved at 3 and 6 months and the cohorts were alike on all demographic descriptors. RPQ average score and symptom occurrence were far more frequent among MTBI patients than for the comparison cohort from 3 to 6 months. The use of health services and indicators of social disruption were also more frequent among MTBI post-discharge patients. Conclusions: These findings argue that some with an MTBI suffer real complaints and they are sustained from 3 to at least 6 months. More effort should be given toward specificity of these symptoms from those reported by members of the comparison group.

Cohort study, comparison cohort, emergency department, inverse probability weighting, outcomes, persistent symptoms, post-concussion, Rivermead Post-Concussion Symptoms Questionnaire

Introduction Post-concussion syndrome has been described as persistent subjective symptoms resulting from cerebral concussion [1]. Unfortunately, ‘persistent’ was not defined as to intensity or duration. The most commonly reported complaints or symptoms include headache, dizziness, irritability, anxiety, blurred vision, insomnia, being easily fatigued and concentration and memory difficulty. While few would argue against the occurrence of these symptoms following a MTBI, many doubt the length or persistence of their duration, hence the controversy. In a 1997 review of the subject, Binder [2] concluded that the effect of MTBI on neuropsychological impact is small and recovery is generally complete by 1–3 months post-injury. Other researchers disagreed, claiming that the effects continued well past 6 months and some claimed they persisted beyond a year [3–6]. It has been pointed out that some factors may ‘influence’ the onset and/or continuation (persistence) of the symptoms following mild brain injury or concussion such as: pending or planned litigation [7–9]; older age [10]; female gender [11];

Correspondence: Jess F. Kraus, Professor Emeritus, Department of Epidemiology, UCLA, 1173 San Marino Drive #4202, San Marcos, CA 92089, USA. Tel: 858-581-8413. E-mail: [email protected]

History Received 16 October 2013 Revised 18 February 2014 Accepted 15 April 2014 Published online 19 May 2014

less education [11]; prior brain injury [3, 12–14]; alcohol abuse [15]; pre-injury psychopathology [1, 9] and malingering [16], among others. The dimensions of persistent symptoms or complaints are their nature, intensity and duration. A full discussion of the nature of symptoms following MTBI is beyond the scope of this report, but the timing of onset and duration or continuity of symptoms is relevant to the broader question of outcomes. The lapse in time after an MTBI and the onset of symptoms in the same person and their persistence are part of the question. For example, those MTBI patients who were symptomatic at 3 months may no longer be symptomatic at 6 months. It is entirely possible that a different sub-set of the MTBI patient group is now reporting symptoms while other members of the original patient group no longer have the symptoms reported at the first assessment. Time to assessment of post-MTBI symptoms or complaints has been inconsistent. While some researchers have assessed symptoms days or 1 or 2 weeks post-injury [17, 18], the most common time intervals have been 1, 3 or 6 months [11, 19, 20]. A few follow-up studies have gone beyond 6 months [21–23]. Symptom persistence (and their assessment) is important, so also is the question of changes in other aspects of the patient’s life following an MTBI such as the need for health

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services and indicators of social disruption. The published literature on this later aspect is very limited, thus this current report includes findings on responses to questions on the types of health services used as well as selected questions on aspects of social disruption or lifestyle attributes. To address health services used and social disruptions as well as follow-up duration inconsistencies and study design shortcomings, a protocol was chosen that incorporated recommendations specified by the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury [24]. That is, outcomes were assessed at 3 and 6 month’s postMTBI with an appropriate comparison group using standard instruments. Hence, the objective of this report was to determine the occurrence of sustained symptoms, health-related services used and social disruptions in a population of adults, aged 18– 64 years, who had a physician diagnosed MTBI identified in one of five collaborating Emergency Departments (ED).

Methods Details about the study population and research design have been published previously [13], but a few relevant aspects are summarized here for clarity. The study population was composed of two Emergency Department (ED) cohorts; MTBI patients vs. comparison non-brain injured patients. Both cohorts were identified in the same time frame from ED trauma logs in five Southern California hospitals and followed simultaneously over a 6-month period. Symptoms or complaints were assessed at 3 and 6 months, consistent with some of the earlier longitudinal studies [19, 23, 25–27]. After triage and with permission from the attending physician, eligible patients were approached in the ED and informed consent was initiated. Once consent was obtained, a detailed in-person interview was administered by trained research staff and permission for further contact was requested. Follow-up phone interviews were conducted at 3 and 6 months from the date of injury. A full description of the all contact procedures and interviews can be found in Kraus et al. [13]. Inclusion/exclusion criteria An MTBI case was defined as a patient, aged 18–64 years inclusive with a head injury from a blow or impact to the head including acceleration/deceleration exposures that resulted in one or more of the following: evidence of transient confusion or disorientation, memory dysfunction, loss of consciousness less than 30 minutes or Glasgow Coma Score (GCS) of 13, 14 or 15 [28]. These inclusion criteria incorporate those recommended by the US Centers for Disease Control (CDC) MTBI Work Group [29]. Members of the comparison non-MTBI cohort must not have had a head trauma at least 1 year before the ED visit, but must have had an Injury Severity Score (ISS) [30] similar to enrolled MTBI patients. The maximum ISS score for all enrolled patients of the study population did not exceed a total of 8 and the maximum head Abbreviated Injury Scale (AIS) for study eligibility was a 1 or 2 for all MTBI patients. Exclusion criteria applied to both cohorts included absence of evidence of trauma, presenting to the ED more than 24 hours post-injury, no phone available for follow-up,

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inability to give informed consent, non-English or Spanish speaking, under police custody during the ED visit or being incarcerated after ED discharge. Use of alcohol or recreational drugs, pre-existing conditions (except those that would preclude successful follow-up) and prior history of or hospitalization for head injury before 1 year of this current ED visit were not factors for exclusion. Survey instruments and administration The baseline questionnaire integrated standardized, previously validated components on demographics, pre-injury lifestyle (general health, living arrangements, alcohol and tobacco consumption, etc.), current employment and preinjury or current morbidities. A data collection form was developed to abstract relevant information from the hospital medical record and included GCS, blood pressure, height and weight, results of any head Computed Tomography (CT) scans or toxicology screenings, procedures and International Classification of Disease diagnostic codes (ICD-9CM) [31]. For purposes of this report, sustained or persistent MTBI symptoms were defined as three or more positive responses [4–6] to the Rivermead Post-Concussion Symptom Questionnaire (RPQ) [32] at 3 and 6 months post-injury. The RPQ is an accepted and validated instrument designed to measure the severity level of 16 symptoms or complaints and its use is consistent with the DSM-IV. This study reports also on responses to five common types of health services used post-injury and five common indicators of social disruption. The reader is referred to Kraus et al. [13] for a full description of the RPQ and health service and social functioning questions. Means and rates per 100 are reported for 3- and 6-month assessments post-injury. Following ED (or hospital) discharge all enrolled patients were contacted by phone as well as postcards at 45 days and again at 135 days post-injury to encourage continued participation. Once a patient’s contact window opened at 3 and 6 months, phone calls were made to administer the study questionnaires. Attempts to contact participants were terminated (as per human subject IRB requirements) if the patient refused to continue, had an invalid or non-operative telephone number or could not be reached after 12 attempts at various daytime or early evening hours on different days of the week. Trained interviewers were blinded as to the cohort status of those contacted. To identify a 50% hypothetical improvement or change in neurologic status from the ED, 318 patients in each cohort needed to be available for a 3-month follow-up interview (at  ¼ 0.05 and power of 0.80). Analysis As reported in an earlier publication [13], Chi-squares or tests-for-trends were undertaken to determine whether any basic differences between groups were statistically significant at the 5% level. Attrition scores were computed using inverse probability weighting. They adjust for baseline differences between the two cohorts and, thus, can reduce the potential bias resulting from differential loss to follow-up [33]. All calculations were performed using SAS 9.2, a statistical software package.

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Institutional review The study protocol was reviewed and approved by the Institutional Review Boards and/or Human Subjects Protection Committees at each participating hospital and also at UCLA.

Results The follow-up telephone interviews required multiple attempts and successful contact at 3 months did not preclude further attempts at 6 months. Among those who completed the 3-month interview, the successful follow-up rate was over 81% for the MTBI cohort and 75% for the Comparison cohort. Features of both study cohorts at baseline, 3 and 6 months are summarized in Table I. There were no significant differences between cohorts in age, gender, race, education, marital status, employment status and history of prior ED visit or hospital admission for injury. The distributions of mechanism of injury and history of head injury remained significantly different between cohorts at 3 and 6 months. Although there was no statistical difference in percentages with a self-reported history of head injury within each cohort at baseline, 3 months and 6 months, there remained a difference between cohorts at baseline, 3 and 6 months. These factors are adjusted in the weighting process described earlier. The percentages of MTBI and Comparison cohort patients who reported any one of the 16 symptoms in the RPQ are shown by rank order in Table II. While the rank order changed

somewhat for both cohorts, the most common symptoms or complaints at 3 months were generally the same at 6 months. MTBI patients reported more of each symptom at 3 months than did patients in the Comparison cohort. The symptom pattern was the same at 6 months. Mean RPQ scores by age and gender for the two cohorts are given in Table III. RPQ scores can range from 0–64 [32], a higher score indicating greater severity. Males in the MTBI cohort at each age group had higher mean scores than males in the Comparison cohort at both 3 and 6 months. Mean scores for the Comparison group of patients at each age interval from 3–6 months showed little difference across most age–gender sub-groups. Positive post-concussion symptoms were defined to be at least three positive responses to any of the 16 questions comprising the RPQ. The overall rate of three or more symptoms per 100 at 3 months for the MTBI cohort was higher than that of patients in the Comparison cohort (Table IV). A similar pattern was observed at 6 months. Three plus symptom rates per 100 at 3 and 6 months are higher for MTBI males at each of the age groups than for males in the Comparison group (Table IV). The same is observed for MTBI females when contrasted with Comparison females. Table V displays 3+ symptom rates per 100 from the RPQ at 3 and 6 months by age group and gender and differs from Table IV in that the 6-month responses are only for those who responded positively or negatively at 3 months. For example,

Table I. Percentage of patients in MTBI and comparison injury cohorts at baseline, 3 months and 6 months post-injury, by selected pre-injury factors. Base (n ¼ 2005) Variable

Category

3 months (n ¼ 1129) p Value

6 months (n ¼ 995)

MTBI

Comp

MTBI

Comp

MTBI

Comp

Age (years)

18–34 35–54 55–64

59.8 32.8 7.4

52.9 38.5 8.6

0.01

54.8 35.3 9.9

49.7 39.9 10.5

p Value 0.23

54.9 35.8 9.3

51.0 38.2 10.8

p Value 0.45

Gender

Male Female

64.5 35.5

62.9 37.1

0.48

63.0 37.0

62.0 38.0

0.72

62.6 37.4

61.7 38.4

0.76

Race

White NH Hisp/Latino Black NH Asian/Other

49.9 29.4 6.0 14.8

51.4 28.2 6.3 14.1

0.88

59.5 23.3 5.3 11.9

57.3 24.0 6.4 12.3

0.84

59.6 22.1 5.3 13.0

56.9 23.8 5.8 13.5

0.86

Education

5HS grad HS grad Some college College/post

14.3 21.3 40.9 23.4

14.6 22.9 36.9 25.6

0.35

9.9 18.4 44.3 27.4

11.8 20.7 39.2 28.3

0.36

10.1 18.1 43.1 28.7

11.7 19.3 30.2 38.8

0.58

Marital status

Married/Sig Single Wid/Div/Sep

40.8 45.9 13.4

43.9 38.3 17.6

50.01

43.2 43.2 13.5

47.3 36.1 16.5

0.05

45.1 43.5 11.4

47.7 36.9 15.4

0.06

Mechanism of injury

Motor vehicle Fall Assault Blunt object

54.2 23.4 11.2 11.2

32.5 30.4 3.9 33.2

50.01

55.8 26.6 7.0 10.6

34.1 29.7 2.4 33.9

50.01

52.3 28.1 7.7 11.9

35.1 29.5 1.9 33.5

50.01

Employment status

Employed Other Unemployed

76.5 12.0 11.5

74.5 13.7 11.9

0.52

78.5 12.6 8.9

76.4 13.9 9.8

0.71

76.9 14.1 9.0

77.2 14.1 8.7

0.99

History of head injury

Yes No

44.9 55.1

38.2 61.8

50.01

45.4 54.6

39.7 60.3

0.06

45.9 54.1

38.5 61.5

0.02

History of ED or hospital

Yes No

53.4 46.6

60.2 39.8

50.01

52.9 47.1

61.7 38.3

50.01

55.7 44.3

60.0 40.0

0.18

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Table II. Rank order of and percentage* with symptoms from the Rivermead Post Concussion Symptom Questionnaire at 3 and 6 months post-injury for the MTBI and Comparison cohorts. 3 Months post-injury MTBI Symptom Fatigue, tiring more easily Sleep disturbance Headaches Forgetfulness, poor memory Feeling frustrated or impatient Taking longer to think Poor concentration Being irritable, easily angered Restlessness Feeling depressed or tearful Feelings of dizziness Noise sensitivity, easily upset by loud noise Light sensitivity, easily upset by bright light Blurred vision Nausea and/or vomiting Double vision

6 Months post-injury

Comparison

MTBI

Comparison

Percentage

Rank

Percentage

Rank

Percentage

Rank

Percentage

Rank

26.2 22.5 22.3 22.0 21.3 19.8 19.1 18.1 17.9 13.7 13.5 9.3 9.1 8.6 6.6 4.2

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

15.8 16.3 11.5 10.7 17.2 10.3 10.0 13.6 8.7 11.0 5.6 5.4 4.8 3.8 4.2 0.6

3 2 5 7 1 8 9 4 10 6 11 12 13 14 15 16

21.3 18.1 22.0 19.8 18.6 16.8 17.0 14.1 12.3 14.1 8.2 10.4 10.7 9.8 5.1 4.3

2 5 1 3 4 7 6 8 10 9 14 12 11 13 15 16

14.8 12.5 9.7 11.5 13.0 9.6 9.9 11.9 8.9 7.9 5.2 4.5 5.4 3.9 3.4 0.8

1 3 7 5 2 8 6 4 9 10 12 13 11 14 15 16

*Percentages will exceed 100 because of multiple choices available for each patient. Table III. Mean Rivermead Post-Concussion Symptoms Questionnaire (RPQ) scores for patients in MTBI and Comparison injury cohorts by age and gender, at 3 and 6 months post-injury. 3 Months post-injury MTBI

6 Months post-injury Comparison

MTBI

Comparison

Age group

Male

Female

Both

Male

Female

Both

Male

Female

Both

Male

Female

Both

18–34 35–54 55–64 All ages

5.61 6.16 5.86 5.82

9.06 10.57 10.17 9.72

6.82 7.80 7.80 7.26

2.95 3.32 2.65 3.06

4.93 5.85 7.22 5.62

3.60 4.42 4.60 4.03

4.37 4.05 6.74 4.45

8.24 8.49 10.33 8.57

5.72 5.75 8.32 5.97

3.08 2.20 3.69 2.84

4.38 5.60 3.70 4.85

3.49 3.75 3.70 3.61

among MTBI males aged 18–34, the 3+ symptom rate at 3 months was 25.4 per 100 persons. At 6 months the 3+ symptom rate was 40 per 100 of those who reported positively at 3 months. The age 55–64 male/female sub-groups were too small in number for meaningful analyses. Similarly, (lower half of Table V) among the other 74.6 per 100 persons with less than three symptoms at 3 months, only 9.1 per 100 reported 3+ symptoms at 6 months. Almost all cells in this section of the table show little difference in lowto-positive conversion in rates for both cohorts—those who were negative at 3 months tended to remain so at 6 months and did not ‘convert’ symptoms development over time. However, many of the age–gender specific rates were based on less than 10 observations in each cell. Changes in rates of reported health services use as well as five indicators of social disruption or functioning are given in Table VI. The services listed are for those with at least 20 persons in each category at 3 months. Six month rates for those who reported positive use at 3 months are given in the top half of the table; the bottom half displays data for those who reported negatively at 3 months. At 6 months over 42 per 100 in the MTBI cohort still reported use of physician’s services out of those who used the same services at 3 months. The health services use rate increased including a 6-fold rise in psychological or mental health counselling.

The rates for selected social disruption indicators reveal several changes from 3 to 6 months. Among those in the MTBI cohort who reported ‘legal representation’ at 3 months, almost two-thirds still had legal representation at 6 months. Also, about three-fourths of those who reported ‘less able to tolerate alcohol’ at 3 months remained so at 6 months. Those in the MTBI group who at 3 months reported no use of any of the health or medical care services listed in Table VI now report use of 3/100–12/100 for the services at 6 months. Finally, MTBI patients who did not indicate a positive response to any of the social indicator questions at 3 months now reported a positive experience at a rate of 5–14 per 100 adults.

Discussion The findings For purposes of this study, sustained or persistent outcomes were defined as 3+ post-concussion symptoms, health service use or social disruption indicators within the same patient at two sequential time periods after discharge from an ED. This definition improves on earlier reports in which ‘persistence’ is implied but not precisely defined, leaving doubt as to the person-to-person continuity of symptoms [21, 34–40]. The rank order of 16 RPQ complaints in cohorts remained somewhat similar from 3 to 6 months. However, it should be

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Table IV. Rate per 100 adults reporting 3+ symptoms from the Rivermead Post Concussion Symptoms Questionnaire for the MTBI and Comparison injury cohorts by age and gender, at 3 and 6 months post-injury. 3 Months post-injury MTBI

6 Months post-injury Comparison

MTBI

Comparison

Age group

Males

Females

Both

Males

Females

Both

Males

Females

Both

Males

Females

Both

18–34 35–54 55–64 All ages

27.89 30.77 21.74* 28.35

43.75 30.91 38.89* 38.56

33.48 30.82 29.27 32.13

13.81 15.53 13.95* 14.45

25.86 25.00 31.25 26.10

17.75 19.65 21.33 18.88

18.66 18.07 42.11* 20.34

42.47 38.46 43.75* 41.13

27.05 25.93 42.86 28.12

17.21 10.85 16.22* 14.96

19.00 24.30 13.33* 20.68

17.78 16.95 14.93 17.15

*Denotes numerator of less than 10.

Table V. Persistency of three or more complaints from the Rivermead Post-Concussion Symptoms Questionnaire, per 100 adults in the MTBI and Comparison cohorts, by age group and gender. MTBI Age group

Male

Comparison

Female

Both

Male

Female

MTBI Both

Male

Female

3+ Symptoms at 3 months 18–34 35–54 55–64 All ages

25.4 31.2 21.1* 27.1

44.4 28.3 40.0* 37.9

18–34 35–54 55–64 All ages

74.6 68.8 79.0 72.9

55.6 71.7 60.0* 62.1

32.0 30.1 29.4 31.1 53 Symptoms 68.0 69.9 70.6 68.9

13.8 12.9 11.4* 13.3 at 3 months 86.2 87.1 88.6 86.8

Comparison Both

Male

Female

Both

3+ Symptoms at 6 months** 25.6 22.3 26.9* 24.3

17.6 17.1 18.0 17.5

40.0 54.2 75.0* 48.3

67.9 76.9 83.3* 72.3

74.4 77.7 73.1 75.7

82.4 82.9 82.0 82.5

9.1* 3.8* 33.3* 9.6

22.9* 12.1* 11.1* 16.9

53.5 68.0 45.5 62.2 33.3* 61.9 80.0* 50.0* 42.9* 59.1 54.6 52.0 3+ Symptoms at 6 months** 13.0 7.0* 25.0* 12.0

9.6 4.0* 6.5* 7.3

9.4* 12.3* 5.3* 10.3

57.5 50.0 45.5* 53.2 9.6 7.5 6.0* 8.3

*Denotes numerator of less than 10. **Denominators for 6-month rates are those who had three or more symptoms at 3 months post-injury.

emphasized that the frequency (or rate) of each complaint is considerably greater in the MTBI patients. A contrast between MTBI and Comparison cohorts on elements of the RPQ showed that headaches, dizziness, forgetfulness, frustration, double vision and fatigue differentiate somewhat the MTBI group from those without a head injury. Information on these factors might be useful for patient screening for possible treatment interventions. Although mean scores from the RPQ show a moderate level of continuing complaints in each of the age–gender subgroups of both cohorts, these values do not indicate withinperson sustained symptoms. It was not possible to track each patient on the basis of each of their own symptoms. Considering the number of potential combinations of symptoms (to define PCS) within each person there would have been far too many data cells for meaningful analyses. This study did track each patient and their overall response to the RPQ. That is, if one patient reported 3+ RPQ symptoms at 3 months that same person was tracked to 6 months. Findings from this current study add new evidence in support of sustained post- concussion symptoms following a physician-diagnosed MTBI. It is reported that symptom, health service use and/or social disruption persistence was present at 6 months for both cohorts, but much more so for those in the MTBI group. While the sustained outcomes rate was not 100% (using either the RPQ or selected common health/medical care services or other social disruption indicators), a sizeable proportion of those with post-MTBI complaints remained so at 6 months, indicating that these

complaints were not transitory, but in all likelihood required the need for medical intervention. Several follow-up studies have reported widely disparate findings, with time intervals from 1 month [40] to 12 months [1, 4, 6, 22] and, in one report [41], from 2–6 weeks up to 8–30 months. Dikmen et al. [21, 22] concluded that long-term effects in hospitalized patients 1 year after discharge were minimal. Rutherford et al. [42] in a 1979 follow-up study of hospitalized patients in England found that 19% reported postconcussion symptoms, but three-quarters of these patients were involved in lawsuits or were judged to be malingering. Levin et al. [43], in a 1987 follow-up study of hospitalized patients with minor head injury, concluded that symptoms identified at 1 month had largely resolved by 3 months. On the other hand, Ponsford et al. [10], in a 2000 study of ED discharged patients, contacted at 1 week and at 3 months using the Rivermead Post-Concussion Checklist [44], found 24% of MTBI patients still had symptoms at 3 months. It was not clear in their report if those who reported symptoms at 1 week were the same persons who reported symptoms at 3 months. (They noted also that there was considerable attrition of study participants from 1 week to 3 months—the study period.) The proportion of control patients with symptoms at 3 months was not reported. These researchers concluded, however, that other factors may have contributed to the post-concussion symptoms reported. In 2003, Savola and Hillborn [41] reported on a follow-up study of Emergency Room admitted patients in Oulu, Finland. A modified RPQ was used to identify PCS in this study.

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Table VI. Persistency of health services use and social disruption indicators per 100 adults in the MTBI and Comparison cohorts. Positive at 3 months Category Have you received services from a . . . ? Physician Physical or occupational therapist, etc. Other services (chiropractor, etc.) Medical outpatient care Psychologist/mental health counselling Since your injury, have you . . . ? Changed your driving practices Changed your employment status Had legal representation from injury Been less able to tolerate alcoholy Received financial public assistance Have you received services from a . . . ? Physician Physical or occupational therapist, etc. Other services (chiropractor, etc.) Medical outpatient care Psychologist/mental health counselling Since your injury, have you . . . ? Changed your driving practices Changed your employment status Had legal representation from injury Been less able to tolerate alcoholy Received financial public assistance

Positive at 6 months**

MTBI

Comparison

MTBI

Comparison

65.4 29.6 21.2 8.9 4.8

60.2 26.8 12.8 5.8 1.9

42.3 42.4 34.9 13.3* 31.2*

41.4 48.6 26.2 16.1* 30.0*

36.2 27.1 30.8 24.3 16.6 9.7 13.9 6.0 11.0 4.3 Negative at 3 months

44.6 26.7 35.0 44.2 63.0 46.2 72.0 25.0* 46.0 21.7* Positive at 6 months**

34.6 70.4 78.8 91.1 95.3

39.8 73.2 87.2 94.2 98.1

12.1 8.0 11.6 6.2 2.8*

14.1 5.8 5.6 2.6 0.8*

63.8 69.3 83.4 86.1 89.0

72.9 75.7 90.3 94.0 95.7

6.1 14.2 4.6 6.8 5.0

6.7 10.5 2.9 2.7* 1.8*

*Denotes numerator of less than 10. **Denominators for 6-month rates are those who were positive at 3-months post-injury. yDenominators are only those who drank alcohol (MTBI ¼ 202, Comparison ¼ 339).

Follow-up was at 1 month and then a second contact was made at 8–30 months post-injury to determine if the symptoms identified at 1 month lasted for more than 1 month (this was the researcher’s definition of persistence). Twentytwo per cent of mild head-injured patients identified at 1 month reported symptoms lasting over 1 month in duration. Unfortunately, there was no comparison group available to assist in interpretation of their findings. Evidence of sustained or persistence in health or medical services utilization was also identified in this current report. This finding supports the observation that MTBI patients not only have continuing post-MTBI problems, impairments or complaints, but their frequency is beyond the prevalence level in the general population as measured in the non-head injured cohort. Based on these findings (and those from earlier studies) there are unfavourable outcomes that follow an MTBI, the problems persist for at least 6 months and a variety of health or medical care services are needed to respond to the outcomes. This information could form the basis for the development of newer guidelines beyond those suggested by Comper et al. [45] on the management of MTBI. Those recommendations include bed rest, counselling, rehabilitation or pharmaceuticals for specific symptoms such as headache. The efficacy of these and other interventions are evaluated in the review by Gravel et al. [46]. Strengths and limitations This paper is one of the few in the peer-reviewed literature that addresses sustained symptoms and health services and indicators of social disruption among MTBI patients using a

comparison cohort recruited from the same EDs. This design can reduce confounding from environmental and other factors. For example, treatment policies in effect at the time of the ED visit would be equally applicable to patients in both cohorts. Outcomes of interest can be compared across cohorts to determine those effects specific to MTBI as opposed to other injuries not to the head. Despite the recruitment and follow-up efforts (which were extensive), the final sample sizes in both cohorts for some symptoms, health services use, social disruption indicators or some agegender groups may not have been large enough for analytic purposes. This study used inverse-probability weighting to adjust for the potential differential dropout in the two cohorts. Taken together, the study design and analysis methods provide some assurance for generalization of the conclusions. Nonetheless, there are shortcomings, some of which have been described in an earlier publication [13]. The present discussion will address those relevant to the issue of outcomes assessment and persistence. The RPQ was selected for this study because of its wide use in many clinical settings and throughout the world. It has been validated [47] at 6 months follow-up and is useful in assessing the severity of emotional, physical and psychological symptoms by telephone. A drawback of the RPQ is that participants self-report on the presence and degree of the symptoms. While it is widely acknowledged that many different factors may influence the reporting of symptoms, the use of the same instrument by both cohorts tempers this criticism somewhat. In addition, the use of non-head injured ED patients as a comparison group (who attending the same

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ED, at the same time and were subject to the same recruitment, data collection and follow-up procedures as the MTBI group) gives some assurance of equality of such factors as stress and perception of injury effects associated with a visit to an ED. Obviously, some degree of self-selection is involved with persons who have sustained a minor injury and choose to visit an ED. There is no reason to believe these factors are not similar between the two cohorts studied. The time intervals used in assessing follow-up (3 and 6 months) were generally consistent with those used in earlier studies, but an additional assessment beyond 6 months would have given more depth to the notion of persistence. However, experience in an earlier study [48] suggested that attrition beyond 6 months would have been extreme considering the large proportion of younger adults with only ‘minor’ injury. This study was able to identify at 3 and 6 months those who had positive responses to the RPQ and to classify the results into those who met the broad criteria of PCS as published in the ICD-10 [49] and in the DMS-IV [50]. The individual mix of symptoms found at 3 months was generally the same at 6 months, based on findings from a very small sample of MTBI and Comparison cohort members. Continuation of this analysis would have been fruitless because of the small sample size issues for each of the extremely large number of possible three, four, five, etc., symptom combinations. While the authors agree with Dean et al. [4] that postconcussion symptoms as currently measured by the RPQ are not sensitive and specific enough for diagnostic use, this instrument does provide insight into the complaints by large numbers of adults who have sustained an MTBI. Even though the bases for reporting MTBI symptoms may rest with factors other than true effects (i.e. malingering, compensation demands) there is no doubt that a substrate of those affected have real problems, need health provider services and sustain changes in their lifestyles. Hence, their identification and treatment should be the priority of relevant healthcare professionals. The consistent finding of shared symptoms between MTBI and non-head injured patients or the non-injured in the general public does not diminish the importance of research into their root causes and resolution. It is now left to determine which factors might best discriminate true effects from MTBI false positives. The size of the problem and its impact on those affected and their families suggest the need for large scale collaborative longitudinal studies with rigorous methods and adequate time post-injury to correctly assess pertinent outcomes. Some patient loss to follow-up was experienced from 3 to 6 months following ED discharge. Study attrition was somewhat more common in patients in the Comparison cohort than for MTBI patients. The attrition weighting procedure, however, adjusts for this small imbalance in the distribution of the two factors involved (history of head injury and mechanism of injury). Furthermore, the issue of under-power due to loss to follow-up may be a concern when results are not significant. However, in this case, this issue is not a concern since the major conclusions are based on consistently greater differences between MTBI and Comparison cohort patients.

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It was not in the scope of this report to discuss all aspects of the myriad of symptoms or their pathogenesis following an MTBI. Readers are referred to the excellent reviews by Iverson [51], Ryan and Warden [39], King [9] and the report prepared by the WHO Collaborating Centre Task Force on MTBI [52] for a cogent discussion of these elements.

Conclusions At 6 months a substantial number of ED-discharged MTBI patient’s still report sustained symptoms as well as health service needs and social disruption beyond those of a comparison group. This suggests that MTBI patients have not achieved ‘normal’ or complete recovery and should be evaluated in more depth. The search for objective rather than subjective measures or tests of minor brain dysfunction as manifested in MTBI patients would aid immensely in the identification of those who are indeed at risk of specific outcomes. Such research should include details of symptom onset, course and resolution. Despite an enormous and growing literature on MTBI outcomes there are still some gaps in the knowledge of its natural history.

Acknowledgements The authors thank the directors of the five Emergency Departments at UCLA, UCI, UCSD Medical Centers and Sharp Memorial and Sharp Chula Vista hospitals who gave of their time and resources to facilitate the identification of research participants and the collection of relevant data. We also thank members of the University of California, Irvine Medical Research Associates Program and staff from Sharp Memorial Hospital Emergency and Trauma Departments for their invaluable assistance with emergency department facilitation and medical records access. The authors also thank the many college students from UCLA and the San Diego area who were extremely helpful with survey administration. This project would not have been successful without the tireless efforts toward participant follow-up by staff from the Southern California Injury Prevention Research Center.

Declaration of interest All authors of this manuscript have no direct financial relationship with any commercial identities mentioned in this paper that might lead to a conflict of interest.

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