Literature DB >> 36247393

Functional outcome, dependency and well-being after traumatic brain injury in the elderly population: A systematic review and meta-analysis.

Rebeca Alejandra Gavrila Laic1, Liedewij Bogaert2, Jos Vander Sloten1, Bart Depreitere3.   

Abstract

Introduction: Traumatic brain injury (TBI) rates in the elderly are increasing worldwide, mainly due to fall accidents. However, TBI's impact on elderly patients' lives has not been thoroughly investigated. Research question: This systematic review and meta-analysis aims at describing post-TBI incidence of functional decline, dependency, nursing home admission, reduced quality of life and depression in the elderly. Materials and methods: A systematic literature search was performed in PubMed, EMBASE, Web Of Science, BIOSIS, Current Contents Connect, Data Citation Index, MEDLINE, SciELO, Cochrane library and CINAHL. Study selection was conducted by two independent reviewers. Meta-analysis was performed using a random-effects model.
Results: Twenty-seven studies were included in the qualitative synthesis and twenty-five in a random-effects meta-analysis. The prevalence of unfavorable functional outcomes after TBI was 65.2% (95% CI: 51.1-78.0). Admission to a nursing home had a pooled prevalence of 28.5% (95% CI: 17.1-41.6) and dependency rates ranged between 16.9% and 74.0%. A reduced quality of life was documented throughout follow-up with SF12/36 scores between 35.3 and 52.3/100.2.6-4.8% of the patients with mild TBI reported depressive symptoms. A large heterogeneity was found among studies for functional outcomes and discharge destination. Discussion and conclusion: In conclusion, elderly patients have a significant risk for functional decline, dependency, nursing home admission and low quality of life following TBI. Moreover, more severe injuries lead to worse outcomes. These findings are important to provide accurate patient and family counseling, set realistic treatment targets and aim at relevant outcome variables in prognostic models for TBI in elderly patients.
© 2021 The Authors.

Entities:  

Keywords:  Dependency; Depression; Elderly; Quality of life; Systematic review; Traumatic brain injury; meta-Analysis

Year:  2021        PMID: 36247393      PMCID: PMC9560680          DOI: 10.1016/j.bas.2021.100849

Source DB:  PubMed          Journal:  Brain Spine        ISSN: 2772-5294


Background

Traumatic brain injury (TBI) is defined as a physical and/or functional injury to the brain caused by an external force (Menon et al., 2010) and its incidence amongst elderly patients has been increasing in the last decades (Mosenthal et al., 2002; Steyerberg et al., 2019; Peeters et al., 2015). Most elderly cases of TBI are classified as mild TBI (Styrke et al., 2007), following the Glasgow Coma Scale (GCS) (Teasdale and Jennett, 1974). However, the term “mild TBI” could be a misnomer, as these patients are particularly at risk for injuries with delayed mass effect and secondary deterioration (Hofman et al., 2001; Stiell et al., 2001; Haydel et al., 2000). Elderly patients, conventionally defined as patients with a chronological age ≥65 years old in most TBI studies (Hawley et al., 2017; Choi et al., 2019; Røe et al., 2015; Susman et al., 2002; Mosenthal et al., 2004; Julien et al., 2017; Deb et al., 1998; Akbik et al., 2019; Erlebach et al., 2017; Haller et al., 2017; Wan et al., 2016; Brazinova et al., 2010), are at risk for a worse recovery after TBI (Mosenthal et al., 2002, 2004; Yu and Richmond, 2005; Thompson et al., 2012; Whitehouse et al., 2016; van Aalst et al., 1991). Poor premorbid condition, neurological sequelae and overall deconditioning lead to an increased risk for psychosocial changes (Rapoport and Feinstein, 2001), disability (Gardner et al., 2018) and secondary medical complications (Thompson et al., 2006). The primary goal of medical management in TBI is to safeguard the patient's Quality of Life (QoL) (Seibert et al., 2002), which can be affected by TBI long after the initial medical treatment phase (Susman et al., 2002; de Guise et al., 2015). However, the lifelong impact of TBI on elderly patients' wellbeing remains a relatively neglected area in the field of TBI-related research to date (Gaastra et al., 2016). Better insight into this matter may help (1) clinicians to set realistic treatment targets, (2) patients and families to gain understanding by improved counseling, and (3) researchers to underpin most relevant outcome determinants in the development of prognostic models for this population. We hypothesize that TBI in elderly patients is associated with a high likelihood of significant functional decline, which easily leads to dependency, and in turn is associated with reduced QoL and depression in this age group (Yu and Richmond, 2005; Rapoport and Feinstein, 2001; Gardner et al., 2018; Albrecht et al., 2015). Therefore, the main objective of the current study is to document risk factors for and incidence of post-TBI functional decline and dependency, nursing home admission, depression and poor QoL in the elderly population.

Methods

Study registration

The protocol for this systematic review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO, registration number [CRD42020212288]) and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) 2020 statement (Page et al., 2021) [Fig. 1] and the Cochrane Handbook for Systematic Reviews of Interventions (Cumpston et al., 2019).
Fig. 1

Prisma flow diagram.

Prisma flow diagram.

Search strategy and study selection

The systematic search was performed in October 2020 in PubMed, EMBASE, Web Of Science (WOS) Core Collection, BIOSIS Citation Index, Current Contents Connect, Data Citation Index, MEDLINE, SciELO Citation Index, the Cochrane Central Register of Controlled Trials and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Language was restricted to English. There was no restriction on publication date. The used MESH (Medical Subject Headings) terms were “Aged”, “Geriatrics'’, ‘‘gerontology’‘, “Nursing Homes”, “Health Services for the Aged”, “Homes for the Aged”, “Housing for the Elderly”, “Brain Injuries, Traumatic”, “qualitative research” and “Case-Control Studies". Studies’ inclusion was limited to clinical, multi-center, case-control or qualitative studies; performed in hospitals, rehabilitation centers and health care facilities for the elderly; including ≥15 patients who sustained a TBI at ≥65 years (as a subset of a broader cohort or as an independent cohort of elderly patients); using one of the assessment instruments included in Appendix A or reporting nursing home admission rates. Studies were excluded if they included patients with a different pre-existing neurological condition or previous alcohol/drugs abuse or did not specifically associate outcomes to the TBI severity (given by the GCS).

Data extraction and analysis

First, references obtained from the systematic search were entered and deduplicated into EndNote X9 (Clarivate Analytics, Philadelphia). Second, titles and abstracts were screened for concordance with the in- and exclusion criteria using Rayyan QCRI software. Full texts of selected studies were then reviewed for final inclusion. The selection process was performed independently by two researchers blinded from each other. Disagreement in results was resolved through mutual discussion. When necessary, a third reviewer was consulted for arbitrage. Data extraction was performed using a standardized data collection form, including the first author's name, publication year, study design, sample size and number of dropouts, TBI injury severity, brain damage location, age of participants, sex of participants, number of months between TBI and assessment, metrics used and outcomes. In case of incomplete or ambiguous data, the corresponding author was contacted via e-mail. All included studies were subjected to descriptive analyses. For studies including a ≥16 years old cohort, only the results of the subset of patients ≥65 years were taken into account.

Quality assessment

The methodological quality of the studies was assessed using the Downs and Black Scale (Downs and Black, 1998) [Appendix B] and classified as excellent (26–27), good (20–25), fair (15–19) and poor (≤14).

Statistical analysis

Two random-effects meta-analyses were conducted using tidyverse, meta and metafor packages in R 4.1.0, using the inverse variance weighted average method (IVW) (Lee et al., 2016), in order to calculate combined prevalences. The DerSimonian and Laird method was used to obtain Tau2 (DerSimonian and Laird, 1986) and the Freeman-Turkey double arcsine transformation method to calculate combined prevalences (Freeman and Tukey, 1950). Clopper-Pearson confidence intervals for individual studies were reported (CLOPPER and PEARSON, 1934). Heterogeneity was quantified using I2 and interpreted as low (0%–30%), moderate (30%–50%), substantial (50%–80%) and considerable (80%–100%) (Cochrane Handbook, 2021). Publication bias was assessed using funnel plots of the combined prevalences.

Results

The database search retrieved a total of 14,407 citations. 11,229 articles were screened by title and abstract and 1974 full-text articles were assessed for eligibility, of which 27 articles were included in the qualitative synthesis [Fig. 1 and Table 1, Table 2, Table 3, Table 4, Table 5] and 25 were meta-analyzed. 40.7% of the included studies had a poor quality and 59.3% a fair quality [Appendix B].
Table 1

Summary of studies which assessed functional outcomes using GOS and GOS-E.

Study (year)TBI severity (given by GCS)ISSType of studyStudy settingsCountryN ​≥ ​65 years oldLOS (days)ComorbiditiesPre-injury anticoagulation (N)Time post-TBI (months)Outcome
Death (%)Persistent vegetative state (%)Severe disability (%)Moderate disability (%)Good recovery (%)
Hawley et al. (2017) (Hawley et al., 2017)AllNRRetrospectiveNational databaseUK575 (439 mild TBI and 136 moderate or severe TBI)65–74 years old: median (IQR)=11(15) 75–84 years old: median (IQR)=14(25) ≥85 years old: median (IQR)=16(23)NRNRHospital discharge143 (24.9%) patients: 35 patients 65–74 years old, 46 75–84 years old and 62≥85 years old. 80 of them had a moderate or severe TBI.29 (5.0%) patients: 11 patients 65–74 years old, 13 75–84 years old and 5 ​≥85 yearsold. 14 of them had a moderate or severe TBI79 (13.7) patients: 27 patients 65–74 years old, 33 75–84 years old and 19 ​≥85 years old. 10 of them had a moderate or severe TBI.358 (62.3%) patients: 127 patients 65–74 years old, 130 75–84 years old and 101 ​≥85 years old. 32 of them had a moderate or severe TBI and 306 had a mild TBI.
Mohindra et al. (2008) (Mohindra et al., 2008)AllNRRetrospectiveHospitalIndia45 ​≥70 years old (5 mild TBI, 7 moderate TBI and 33 severe TBI)NRNRNR65 (71.4%) patients with moderate TBI and 24 (72.7%) of the patients with severe TBI1 (14.3%) patients with moderate TBI and 8 (24.2%) of the patients with severe TBI1 (20.0%) patients with mild TBI4(80.0%) patients with mild TBI, 1 (14.3%) of the patients with moderate TBI and 1 (3.0%) patient with severe TBI
Choi et al. (2019) (Choi et al., 2019)All21 patients minor (1–8); 53 moderate (9–15); 56 serious (16–24); 40 severe (≥25)RetrospectiveRepublic of Korea170 (129 mild TBI, 15 moderate TBI and 26 severe TBI)NRNRNR68 (6.2%) patients with mild TBI, 8 (53.3%) with moderate TBI and 23 (88.5%) with severe TBI118 (91.5%) patients with mild TBI, 10 (66.7%) with moderate TBI and 3 (11.5%) with severe TBI
Mosenthal et al. (2004) (Mosenthal et al., 2004)MildNRRetrospectiveMulti-centerUS44NRNRNRHospital dischargeUnknownUnknownUnknownUnknown13 (29.5%)
Julien et al. (2017) (Julien et al., 2017)MildMedian=25 (results only reported for 952 patients)RetrospectiveHospitalCanada982Median (IQR)=11 (17)NR439 (44.7%)Hospital discharge162 (16.5%)31 (3.2%)256 (26.1%)508 (51.7%)24 (2.4%)
Deb et al. (1998) (Deb et al., 1998)MildNRRetrospectiveHospitalUK40NRNRNR120 (0.0%)0 (0.0%)1 (2.5%)12 (30.0%)
Akbik et al. (2019) (Akbik et al., 2019)Moderate and severeNRRetrospectiveLevel I trauma centerUS62 (31 GCS >9 and 31 GCS≤9)Median=937 patients hypertension, 10 atrial fibrillation, 12 diabetes, 14 coronary artery disease, 8 CVA, 8 neoplastic process, 7 dementia37Hospital discharge24 (38.7%) patients with a mean GCS ​= ​7.81 ​±4.094 (6.5%) patients with a mean GCS ​= ​7.81 ​±4.0926 (41.9%) patients with a mean GCS=11.16± ​3.66 (9.7%) patients with a mean GCS=9.86±4.342 (3.2%) patients with a mean GCS=9.86±4.34
Erlebach et al. (2017) (Erlebach et al., 2017)Moderate and severeMedian (IQR)=20 (11)RetrospectiveHospitalSwitzerland509.2±8.5 (in ICU)1 patient stroke, 5 TBI, 1 epilepsy, 10 diabetes, 35 cardiovascular diseases, 4 psychiatric disorder and 8 alcohol/drug abuse27640 (80.0%)10 (20.0%)
Gritti et al. (2019) (Gritti et al., 2019)Moderate and severeNRRetrospectiveHospitalItaly38 ​≥70 years oldNR15 patients diabetes and 27 hypertension351215 (39.5%)1(2.6%)8 (21.0%)7(18.4%)7(18.4%)
Won et al. (2017) (Won et al., 2017)SevereNRRetrospectiveSingle centerGermany29 ​≥80 years old9.1±6.259 patients hypertension, 30 atrial fibrillation, 26 type 2 diabetes, 44 cardiovascular diseases, 20 respiratory insufficiency, 14 renal failure, 8 hematological disease, 51 metabolic disease, 8 previous stroke, 34 pneumonia, 3 sepsis51Hospital discharge23 (79.3%)6 (20.7%)
Tokutomi et al. (2008) (Tokutomi et al., 2008)SevereMean (SD)= 26 (9)RetrospectiveNational databaseJapan189> ​70 years oldNR52.4% of the casesNR3–6131 (69.3%)17 (9.0%)22 (11.6%)9 (4.8%)
Haller et al. (2017) (Haller et al., 2017)SevereMedian (IQR)=25 (12)Prospective observationalMulti-centerSwitzerland97NR10 patients psychiatric disorders and 16 alcohol abuse263, 6 and 12Mean GOS-E 6 (range 3–8) at 3 and 6 months, and mean GOS-E 7 (range 5–8) at 12 monthsUnknown
Wan et al. (2016) (Wan et al., 2016)SevereNRRetrospectiveHospitalChina328NR51 patientsNR660 (18.3%)77 (23.5%)35 (10.7%)
Brazinova et al. (2010) (Brazinova et al., 2010)SevereMedian=20Prospective observationalMulti-centerAustria, Bosnia and Herzegovina, Croatia, Macedonia, and Slovakia100NRNRNR1289 (89.0%)11 (11.0%)
Røe et al. (2015) (Røe et al., 2015)SevereNRProspective observationalMulti-centerNorway97 (46 patients 65–74 years old and 51 ​≥71 years old)NRPresent in 35 patients 65–74 years old and 45 patients ≥75 years old21 patients 65–74 years old and 37 patients ≥75 years old1220 (44.0%) the patients 65–74 years old and 44 (86.0%) patients ≥75 years old26 (56.0%) patients 65–74 years old and 7 (14 .0%) patients ≥75 years old

N=number; GCS=Glasgow Coma Scale; All=Mild, moderate and severe TBI; ISS=Injury Severity Score; NR=not reported; LOS=length of hospital stay due to TBI; CVA=cerebrovascular accident; Severe disability=GOS of 3 or GOS-E of 3 or 4; Moderate disability= GOS of 4 or GOS-E of 5 or 6; Good recovery= GOS of 5 or GOS-E of 7 or 8; UK=United Kingdom; US=United States of America.

Table 2

Summary of studies which assessed ADL dependency after TBI using FIM.

Study (year)TBI severity (given by GCS)ISSType of studyStudy settingsCountryN ​≥ ​65 years oldLOS (days)ComorbiditiesPre-injury anticoagulationTime post-TBI (months)Outcomes
FIM motor (mean)FIM cognition (mean)FIM total (mean)
Mosenthal et al. (2004) (Mosenthal et al., 2004)MildNRRetrospectiveMulti-centerUS44NRNRNRHospital discharge and 627 (61.4%) total independence at hospital discharge and at 6 months, 3 patients (6.8%) worse FIM than at discharge, 20 patients (45.5%) unchanged FIM and 9 patients (20.5%) improved FIM
Susman et al. (2002) (Susman et al., 2002)Moderate and severe (mean GCS 8.7)Mean ​± ​SD= 17.4± ​8.7Retrospective observational studyDatabaseUS3244NRNRNRHospital dischargeAbnormal FIM locomotion: 1161 patients (35.8%)
Abnormal FIM expression: 548 patients (16.9%)
Abnormal FIM feeding: 1090 patients (33.6%)
Lecours et al. (2012) (Lecours et al., 2012)SevereNRRetrospective observational studyLevel I and level II trauma centerCanada95 (44 patients 65–74 years old, 42 75–84 years old and 9 ​≥85 years old)NRNRNR24–4842.6 (SD 9.5): 40.5 (SD 11.6) in the 65–74 years old, 41.5 (SD 10.5) in the 65–74 years old and 41.0 (SD 17.0) in the ≥85 years old17.8 (SD 5.4)Unknown

N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS=length of hospital stay due to TBI; US=United States of America.

Table 3

Summary of studies which assessed ADL dependency and integration using CIQ, OARS and non-standardized assessments.

Study (year)TBI severity (given by GCS)ISSType of studyStudy settingsCountryN ​≥ ​65 years oldLOS (days)ComorbiditiesPre-injury anticoagulationTime post-TBIType of assessmentOutcomes
Kinsella et al. (2014) (Kinsella et al., 2014)MildNRRetrospectiveHospitalAustralia50Median (IQR)=4 (5)NRNR3 monthsCIQCIQ home mean 5.8 (SD 2.9); CIQ social 8.3 (SD 2.6)
Brousseau et al. (2017) (Brousseau et al., 2017)MildNRProspective observationalMulti-centerCanada344NR0-1 comorbidities in 51 patients,2–4 in 148 and 5–13 in 143NR6 monthsOARS24 patients (7.0%) had functional decline
Thompson et al. (2012) (Thompson et al., 2012)Mild65–74 years old: mean (SD)=17.9 (11.7 75–84 years old: mean (SD)= 7.5 (10.9)RetrospectiveNational databaseUS309NRIn the 65–74 years group: 42.9% of the patients CCI=0, 28.4% CCI=1, 14.5% CCI=2 and 14.2% CCI≥3 In the 75–84 years group: 28.8% CCI=0, 29.6% CCI=1, 17.0% CCI=2, 24.6% ​≥3NR12 monthsInterview/non-standardized assessmentIn the 65–74 years group patients had by mean 1.3 (SD 2.7) ADL difficulties and in the 75–84 years group a mean of 2.2 (SD 3.2). The number of ADL difficulties pre-injury was 0 in 87% of the 65-74 years-old patients and 71.5% of the 75-84 years-old patients
Miller et al. (2017) (Miller et al., 2017)Mild and moderateNRRetrospectiveNational databaseUS36288NRNRNRHospital dischargeInterview/non-standardized assessment76.0% of the 70–79 years old group, 67.0% of the 80–89 years old group and 61.0% of the ≥90 years old group were independent at discharge
Lilley et al. (2016) (Lilley et al., 2016)SevereMedian (IQR)= 5 (10)RetrospectiveNational databaseUS90Median (IQR)=8 (14)41.9% CCI=0, 30.2% CCI=1, 16.3% CCI=2, 11.6 CCI ≥378.3% of the patientsHospital dischargeInterview/non-standardized assessment61 patients (67.8%) were dependent for one or more ADL
Lecours et al. (2012) (Lecours et al., 2012)SevereNRRetrospectiveLevel I and level II trauma centerCanada95NRNRNR24–48 monthsInterview/non-standardized assessment69 of 136 participants (>55 years old) needed no help to transfer to chair, wheelchair, or bed and 79 of 136 participants (>55 years old) needed minimal help for going up or down the stairs

N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS= length of hospital stay due to TBI; CCI=Charlson Comorbidity Index; US=United States of America.

Table 4

Summary of studies which addressed nursing home admission after TBI.

Study (year)TBI severity (given by GCS)ISSType of studyStudy settingsCountryN ​≥ ​65 years oldLOS (days)ComorbiditiesPre-injury anticoagulation (N)Time post-TBI (months)Outcomes
N patients discharged to a nursing home (%)
Khan et al. (2017) (Khan et al., 2017)MildMedian (IQR)=17 (11)RetrospectiveNational databaseUS8750NRNRNRHospital discharge2993 (34.2%)
Schmidt et al. (2019) (Schmidt et al., 2019)MildNRRetrospectiveLevel I trauma centerSwitzerland344 (141 patients 65–74 years old, 125 75–84 years old and 78 ​≥85 years old)Mean (SD)=2(2)9.3% of the patients had diabetes, 22.7% psychiatric diseases and 5.2% musculoskeletal diseasesNRHospital discharge20 (5.8%): 1 patient 65–74 years old, 6 75–84 years old and 13 ​≥85 years old
Velez et al. (2020) (Velez et al., 2020)MildMedian=11RetrospectiveNational databaseUS19664NRMedian CCI=4NRHospital discharge5821(29.6%)
Thompson et al. (2012) (Thompson et al., 2012)Mild65–74 years old: mean (SD)=17.9 (11.7) 75–84 years old: mean (SD)= 7.5 (10.9)RetrospectiveNational databaseUS309NRIn the 65–74 years group: 42.9% of the patients CCI=0, 28.4% CCI=1, 14.5% CCI=2 and 14.2% CCI≥3 In the 75–84 years group: 28.8% CCI=0, 29.6% CCI=1, 17.0% CCI=2, 24.6% ​≥3NR12108 (35.0%), of which 10.4% were 65–74 years old and 24.6 75–84 years old
Miller et al. (2017) (Miller et al., 2017)Mild and moderateNRRetrospectiveNational databaseUS36288NRNRNRHospital discharge∗76.0% of the 70–79 years old group, 67.0% of the 80–89 years old group and 61.0% of the ≥90 years old group were discharged to home or prison
Bhullar et al. (2010) (Bhullar et al., 2010)Moderate65–80 years old: mean=12 ​>80 years old: mean=11RetrospectiveLevel II trauma centerUS328NRNRNRHospital discharge27 (8.2%)
Gorman et al. (2020) (Gorman et al., 2020)Moderate and severeMedian (IQR)= 17 (9)RetrospectiveNational databaseUS3292NRMedian CCI=4NRHospital discharge931 (28.3%)
Susman et al. (2002) (Susman et al., 2002)Moderate and severe (mean GCS=8.7)Mean ​± ​SD= 17.4± ​8.7RetrospectiveDatabaseUS3244NRNRNRHospital discharge1752 (54.0%)
Lilley et al. (2016) (Lilley et al., 2016)SevereMedian (IQR)= 5 (16–26)RetrospectiveNational databaseUS90Median (IQR)=8 (14)41.9% CCI=0, 30.2% CCI=1, 16.3% CCI=2, 11.6 CCI ≥378.3%Hospital discharge61 (67.8%)
Haller et al. (2017) (Haller et al., 2017)SevereMedian (IQR)=25 (12)Prospective observationalMulti-centerSwitzerland97NR10 patients psychiatric disorders and 16 alcohol abuse26310 (10.3%) at 3 months, 14 (14.4%) at 6 months and 16 (16.5%) at 12 months
Røe et al. (2015) (Røe et al., 2015)SevereNRProspective observationalMulti-centerNorway97 (46 65–74 years old and 51 ​≥75 years old)NR35 patients 65–74 years old and 45 patients ≥75 years old21 65–74 years old and 37 p ≥75 years old125 (5.2%): 4 patients 65–74 years old and 1 patient ≥75 years old
Lecours et al. (2012) (Lecours et al., 2012)SevereNRRetrospectiveLevel I and level II trauma centerCanada95NRNRNR24–4821 (22.1%)

N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS= length of hospital stay due to TBI; CCI=Charlson Comorbidity Index; US=United States of America.

Table 5

Summary of studies which addressed QoL after TBI.

Study (year)TBI severity (given by GCS)ISSType of studyStudy settingsCountryN ​≥ ​65 years oldLOS (days)ComorbiditiesPre-injury anticoagulationTime post-TBI (months)Type of assessmentOutcomes
Kinsella et al. (2014) (Kinsella et al., 2014)MildNRRetrospectiveHospitalAustralia50Median (IQR)=4 (5)NRNR6SF-12Mean SF-12 PCS score 36.71 (SD 10.7); mean SF-12 MCS score 53.2 (SD 8.8)
Thompson et al. (2012) (Thompson et al., 2012)Mild65–74 years old: mean (SD)=17.9 (11.7 75–84 years old: mean (SD)= 7.5 (10.9)RetrospectiveNational databaseUS309NRNRNR12SF-36 and SF-6DMean SF-36 PCS score: 39.5(SD 17.2) in the 65–74 years old group and 35.3 (SD 17.4) in the 75–84 years old group
Mean SF-36 MCS score: 51.7 (SD 16.5) in the 65–74 years old group and 48.2(SD 18.4) in the 75–84 years old group
Mean SF-6D: 0.73 (SD 0.25) in the 65–74 years old group and 0.67 (SD 0.26) in the 75–84 years old group
Haller et al. (2017) (Haller et al., 2017)SevereMedian (IQR)=25 (12)Prospective observationalMulti-center studySwitzerland97NR10 patients psychiatric disorders, 16 alcohol abuse26 patients3, 6 and 12SF-12Mean SF-12 PCS score 39.2 (range 30.7–50.0); mean SF-12 MCS score 52.3 (range 44.7–55.7) at 3 months, mean SF-12 PCS score 42.3 (34.9–52.8); mean SF-12 MCS score 51.2 (45.3–57.1) at 6 months and mean SF-12 PCS score 44.2 (34.3–52.8); mean SF-12 MCS score 52.3 (45.8–57.2) at 12 months

N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS= length of hospital stay due to TBI; US=United States of America.

Summary of studies which assessed functional outcomes using GOS and GOS-E. N=number; GCS=Glasgow Coma Scale; All=Mild, moderate and severe TBI; ISS=Injury Severity Score; NR=not reported; LOS=length of hospital stay due to TBI; CVA=cerebrovascular accident; Severe disability=GOS of 3 or GOS-E of 3 or 4; Moderate disability= GOS of 4 or GOS-E of 5 or 6; Good recovery= GOS of 5 or GOS-E of 7 or 8; UK=United Kingdom; US=United States of America. Summary of studies which assessed ADL dependency after TBI using FIM. N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS=length of hospital stay due to TBI; US=United States of America. Summary of studies which assessed ADL dependency and integration using CIQ, OARS and non-standardized assessments. N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS= length of hospital stay due to TBI; CCI=Charlson Comorbidity Index; US=United States of America. Summary of studies which addressed nursing home admission after TBI. N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS= length of hospital stay due to TBI; CCI=Charlson Comorbidity Index; US=United States of America. Summary of studies which addressed QoL after TBI. N=number; GCS=Glasgow Coma Scale; ISS=Injury Severity Score; NR=not reported; LOS= length of hospital stay due to TBI; US=United States of America.

Demographic and study characteristics

The included studies were retrospective or prospective observational studies performed in single or multi-center settings, or based on regional or national databases. The number of included patients ranged between 29 and 36,288. Follow-up duration across studies ranged from hospital discharge to 4 years post-TBI [Table 1, Table 2, Table 3, Table 4, Table 5].

Functional outcome

Functional outcome was assessed using the Glasgow Outcome Score (GOS) and the Extended Glasgow Outcome Score (GOS-E) in 15 studies [Table 1], of which 14 could be meta-analyzed [Fig. 2, Fig. 3].
Fig. 2

Meta-analysis results for unfavorable functional outcomes.

Fig. 3

Funnel plot for the studies used in the unfavorable functional outcomes meta-analysis.

Meta-analysis results for unfavorable functional outcomes. Funnel plot for the studies used in the unfavorable functional outcomes meta-analysis. GOS is scored following a scale where 1 corresponds to death, 2 to vegetative state, 3 to severe disability, 4 to moderate disability and 5 to good recovery (Jennett and Bond, 1975). GOS-E is scored as: 1 (death), 2 (vegetative state), 3 (lower severe disability), 4 (upper severe disability), 5 (lower moderate disability), 6 (upper moderate disability), 7 (lower good recovery) to 8 (upper good recovery) (Wilson et al., 1998). GOS 1–3 and GOS-E 1–4 are considered as unfavorable outcomes. Results are visualized in Fig. 4.
Fig. 4

Mean rates of unfavorable functional outcomes for the different TBI severities at different follow-up time points.

Mean rates of unfavorable functional outcomes for the different TBI severities at different follow-up time points. The pooled prevalence of unfavorable outcomes was 65.2% (95% CI: 51.1–78.0) at 12 months post TBI in mild, moderate and severe TBI patients. A significant heterogeneity between studies was found (I2=97%, p<0.01) [Fig. 2, Fig. 3] and the asymmetric funnel plot indicates publication bias [Fig. 3]. In patients with mild TBI, 45.8% had unfavorable outcomes at hospital discharge, including 16.5% who died (Julien et al., 2017). Rates of good recovery at discharge after mild TBI varied between 2.4 and 71.0% (Hawley et al., 2017; Mosenthal et al., 2004; Julien et al., 2017). At 6 months post mild TBI, rates of unfavorable outcomes between 6.2 and 20% were reported (Choi et al., 2019; Mohindra et al., 2008), while these were of 2.5% at 1 year (Deb et al., 1998). For moderate TBI, at 6 months FU, 53.3–85.7% had unfavorable outcomes (Choi et al., 2019; Mohindra et al., 2008), and for moderate and severe TBI combined the 6 months unfavorable outcome rate reportedly was 80.0% (Erlebach et al., 2017). For patients who sustained severe TBI, outcomes were unfavorable in 79.3% at hospital discharge (Won et al., 2017), 41.8–89.9% 3–6 months post TBI (Choi et al., 2019; Wan et al., 2016; Tokutomi et al., 2008) and 72.2–89.0% 1 year post-TBI (Røe et al., 2015; Brazinova et al., 2010). Differences regarding recovery in patients with mild TBI were observed across studies performed in different regions. While Mohindra et al. (2008) and Julien et al. (2017) reported very low or unexisting ‘‘good recovery’’ rates in India and Canada, respectively, higher recovery rates were reported by Hawley et al. (2017), Choi et al. (2019) and Mosenthal et al. (2004) in the United Kingdom (UK), Korea and United States (US).

Activities of daily living (ADL) dependency and social integration

ADL dependency was assessed in 8 studies using the Functional Independence Measure (FIM), Older Americans' Resources and Services scale (OARS) (Milligan et al., 1988), the Community Integration Questionnaire (CIQ) (Willer et al., 1994) and non-standardized evaluations [Table 2, Table 3]. FIM is an 18-item functional assessment scale containing a motor and cognitive domain. Motor scores range between 13 (lowest) and 91 (highest level of independence), cognitive scores between 5 (lowest) and 35 (highest level of independence) and total score between 18 (lowest) and 126 (highest level of independence) (Linacre et al., 1994). OARS is a 28-point questionnaire which assesses different ADL activities, scored on a 0–2 scale. Scores range between 0 (complete dependency) and 28 (complete independency) (Milligan et al., 1988). The CIQ is a 15-item questionnaire which assesses home integration, social integration and productive activity. Total scores range from 0 (low integration) to 29 points (high integration), with a maximum score of 10 points for home integration, 12 points for social interaction and 7 points for productive activity (Willer et al., 1994). In patients with mild TBI, at hospital discharge, a dependency rate of 38.6% was registered (Mosenthal et al., 2004). At 6 months follow-up, Brousseau et al. (2017) found a functional decline in 7.0% of the patients, defined as a reduction of 3 points on the OARS scale from their emergency department visit to FU, while on the other hand Mosenthal et al. (2004) showed an improvement in FIM scores in 20.5% of the patients at 6 months post mild TBI. At 1 year follow-up, 65-74 year-old patients had an average of 1.3 ADL difficulties and 75-84 year-old patients an average of 2.2 ADL difficulties (Thompson et al., 2012). Considering patients with mild and moderate TBI, Miller et al. (2017) found that at hospital discharge 24.0% of the patients 70–79 years old, 33.0% of the patients 80–89 years old and 39.0% of the patients ≥90 years old were dependent. For patients with moderate and severe TBI, at hospital discharge Susman et al. reported dependency rates of 35.8%, 16.9% and 33.6%, for motor function, expression and feeding, respectively (Susman et al., 2002). For severe TBI cases, Lilley et al. found that 67.8% of the patients were dependent for one or more ADL activities at hospital discharge (Lilley et al., 2016). At 2–4 years FU, 74.0% of the patients were dependent for mobility, of which 49.3% needed help for transfers and 41.9% needed help for climbing stairs, and 73.0% were dependent for self-care (Lecours et al., 2012).

Discharge destination

Discharge destination from hospital discharge to 4 years post TBI was reported in 12 articles [Table 4]. In patients with mild TBI, 5.8%–34.2% were discharged to a nursing home (Thompson et al., 2012; Schmidt et al., 2019; Velez et al., 2020; Khan et al., 2017) and 35.0% continued residence beyond one year (Thompson et al., 2012). Considering patients with mild and moderate TBI, Miller et al. (2017) found that 24.0% of the 70-79 years-old, 33.0% of the 80-89 years-old and 39.0% of the ≥90 years-old patients were discharged to an institution (Miller et al., 2017). Rates of nursing homes discharge ranged between 28.3 and 54.0% in studies considering both moderate and severe TBI (Susman et al., 2002; Gorman et al., 2020). In patients with severe TBI, this rate was 67.8% at hospital discharge (Lilley et al., 2016), 10.3% at 3 months, 14.4% at 6 months (Haller et al., 2017), 5.1–16.5% at 12 months (Røe et al., 2015; Haller et al., 2017) and 22.1% at 24–48 months (Lecours et al., 2012). Similar rates of nursing home admissions for patients with mild TBI were reported by Khan et al. (2017), Velez et al. (2020) and Thompson et al. (2012) in the US, which were higher than the rate reported by Schmidt et al. (2019) in Switzerland. No similarities were found in studies conducted in the US for patients with moderate and severe TBI (Thompson et al., 2012; Gorman et al., 2020; Bhullar et al., 2010). A high heterogeneity between studies was found in the 12 meta-analyzed studies (I2 =100%, p<0.01) [Fig. 5, Fig. 6]. The asymmetric funnel plot indicates publication bias [Fig. 6]. The pooled prevalence of nursing home admission was of 28.5% (95% CI: 17.1–41.6).
Fig. 5

Meta-analysis results for nursing home admissions.

Fig. 6

Funnel plot for the studies used in the nursing home admissions meta-analysis.

Meta-analysis results for nursing home admissions. Funnel plot for the studies used in the nursing home admissions meta-analysis.

QoL

QoL was assessed using the 12-Item Short Form Survey (SF-12) (Ware et al., 1996), 36-Item Short Form Survey (SF-36) (Ware and Sherbourne, 1992) and Six-dimensional health state short form (SF-6D) (Ferreira et al., 2013) in 3 studies [Table 5 and Fig. 7].
Fig. 7

Mean MCS and PCS scores for the different TBI severities at different follow-up time point.

Mean MCS and PCS scores for the different TBI severities at different follow-up time point. SF-12 (Ware et al., 1996) and SF-36 (Ware and Sherbourne, 1992) assess the impact of health on patients’ everyday life on a scale ranging between 0 (low QoL) and 100 (high QoL). Both questionnaires contain a Physical Component Summary (PCS) and a Mental Component Summary (MCS) (Ware et al., 1996; Ware and Sherbourne, 1992). The average reported population score is 50 (Huo et al., 2018; Maglinte et al., 2012). SF-6D evaluates role participation, social functioning, bodily pain, mental health and vitality (Ferreira et al., 2013). Scores range between 0.0 (worst health state) to 1.0 (best health state) (Ferreira et al., 2013). In patients with mild TBI, Kinsella et al. reported an average PCS score of 36.7 (Kinsella et al., 2014), and average MCS of 52.1 ​at 6 months follow-up (Kinsella et al., 2014). At 12 months, Thompson et al. reported PCS SF-12 scores of 39.5 for the 65–74 year old patients and 35.3 for the 75–84 year olds (Thompson et al., 2012), while average MCS scores were 51.7 for the 65–74 year old patients and 48.2 for the 75–84 year olds (Thompson et al., 2012). In severe TBI cases, Haller et al. found a mean SF-12 PCS score of 39.2 and a mean MCS score of 52.3 ​at 3 months, a mean PCS score of 42.3 and mean MCS score of 51.2 ​at 6 months, and a mean PCS score of 44.2 and mean MCS score of 52.3 ​at 12 months (Haller et al., 2017).

Depression

One study retrospectively studied depression 1 year post mild TBI in 309 patients ≥65 years old from a national database in US (Thompson et al., 2012). Assessment was performed through the self-report question: ‘‘Before your injury, did a doctor ever tell you that you had depression?’’ and through the Center for Epidemiologic Studies Depression Scale-Revised at follow-up, which is a 20-item questionnaire whose scores range from 0 to 60 (Eaton et al., 2004). Higher scores indicate the presence of more depressive symptomatology (Eaton et al., 2004). One year after mild TBI, depressive symptoms were found in 4.8% of the 65–74 years old patients and 2.6% of the 75–84 years old patients (Thompson et al., 2012).

Discussion

This study assesses QoL, functional outcome, dependency, nursing home admission rate and incidence of depression in elderly patients of ≥65 years old who sustained TBI. The results show a prevalence for unfavorable functional outcomes of 65.2% (95% CI: 51.1–78.0) and a prevalence of nursing home admission of 28.5% (95% CI: 17.1–41.6). Dependency rates range between 16.9% and 74.0%, with outcomes worsening with increasing severity and age and with unclear recovery over time. QoL was found to be particularly decreased as indicated by reported PCS scores ranging between 35.3 and 44.2/100 ​at 3–12 months post TBI. This is far below the population average scores (50/100 (Huo et al., 2018; Maglinte et al., 2012). In contrast, the MCS scores were similar to the population average scores, ranging between 48.2 and 52.3/100 ​at 6–12 months follow-up. 2.6–4.8% of patients with mild TBI reported depressive symptoms. Higher injury severity was associated with poorer functional outcomes. However, this is not the case for QoL, where only subtle differences were observed between patients with mild and severe TBI and, in some cases, the reported QoL scores were lower for patients with mild TBI. To date, there is a relative scarcity of evidence and lack of detail in studies reporting on elderly TBI outcomes (Steyerberg et al., 2019; Peeters et al., 2015). Particularly, only three studies investigated QoL in elderly patients. While dependency in ADL is a strong predictor of declining QoL (Enkvist et al., 2012; WILHELMSON et al., 2005), the relation between mood changes and function is not straightforward. As the safeguarding of acceptable QoL is the primordial goal of any medical treatment, documented QoL outcomes following TBI in elderly are of major importance for treatment guidance and counseling. Nevertheless, to date, we could find no guidelines on the management of TBI in the elderly. We hypothesized that TBI in elderly patients often results in significant functional decline and poor QoL, and the obtained results seem to confirm this. Moderate and severe TBI have a significant impact on dependency and QoL in elderly, while mild TBI has a potentially strong impact. Interestingly, Haller et al., Kinsella et al. and Thompson et al. found that health-related QoL was impaired to the same extent in mild as in severe TBI (Haller et al., 2017; Thompson et al., 2012; Kinsella et al., 2014). This might be explained by the definition of ‘‘mild TBI’‘, following the GCS, not being sufficiently reliable in elderly patients. These patients are at a particular risk of deterioration after hospital admission (Hofman et al., 2001; Stiell et al., 2001; Haydel et al., 2000) and, therefore, the impact of mild TBI should not be underestimated. Furthermore, we believe that QoL depends on a large amount of factors about the patients' lives and not only the patients' status after TBI. This could lead, in some cases, to subjective results. Therefore, it could be that in some cases patients with mild TBI potentially perceive their limitations as a serious burden, while patients surviving moderate and severe TBI may be rather positive, outweighing the disabilities by their happiness to be still alive. A limitation of the current study is the scarcity of published literature documenting outcomes of TBI in elderly, particularly in terms of QoL and depression. Moreover, the review was limited to studies written in English. However, the main limitation is the inter-study variability in outcome scales used, study settings and timings of assessment applied. Furthermore, the included studies generally contained insufficient detail to correct for patients’ heterogeneity, comorbidities, injury characteristics and clinical management in this population. An attempt to compare studies with similar characteristics has been performed. However, this has not been possible in all the cases due to the variability in outcome scoring, in combination with the impossibility for actual stratification. The establishment and application of an international reporting standard would be very useful. Finally, if all the included studies would have contained more detail on patient and injury characteristics and management, this could have enabled a meta-analysis for all the included outcomes, which was not possible. The results from this review illustrate the major burden of TBI in the elderly, primarily for the patients and their families. Second, to society, which is reflected in needs for outpatient supplies and residential care facilities and associated costs. In contrast, research in this field is, to date, rather limited and no clinical guidelines for the management of elderly TBI exist. Better insight into outcomes and risk factors for poor outcome, ideally resulting in the development of prognostic models specific for elderly TBI, can improve counseling of patients and their families, and help caregivers to set realistic treatment targets, particularly in situations of severe TBI where often surgical decisions need to be made fast and treatment withdrawal might be a humane alternative. Further clinical research in this field is therefore urgently needed in order to facilitate clinical guideline development.

Conclusion

TBI in the elderly has a major impact on patients’ lives, often leading to functional decline, dependency, nursing home admission and poor QoL. This is particularly true in moderate and severe TBI, but potentially also true in mild TBI. Older age and injury severity are risk factors for poor functional outcome, while poor QoL is seen in all severities of TBI.

Authorship confirmation statement

All authors contributed to the study conception and design. The articles screening and selection was performed by Rebeca Alejandra Gavrila Laic and Liedewij Bogaert. Studies' quality assessment and data extraction was performed by Rebeca Alejandra Gavrila Laic. The first draft of the manuscript was written by Rebeca Alejandra Gavrila Laic and Bart Depreitere. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Author(s’) disclosure statement(s)

The authors declare that they have no competing interests.

Funding statement

This work was supported by and Helaers foundation.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Assessment techniqueOutcome
WHO Disability Assessment Schedule (WHODAS)Functional outcome
Functional Independence Measure (FIM)Functional outcome
Glasgow Outcome Scale (GOS)Functional outcome
GOS-Extended (GOS-E)Functional outcome
Disability Rating Scale (DRS)Functional outcome
Functional Assessment Measure (FAM)Functional outcome
Functional Status Examination (FSE)Functional outcome
Community Integration Questionnaire (CIQ)Functional outcome
Barthel IndexFunctional outcome
Patient Reported Outcomes Measurement Information System (PROMIS)Functional outcome
Rivermead Postconcussion Symptoms QuestionnaireFunctional outcome/depression
Trauma outcome profile (TOP)Functional outcome/depression
European Brain Injury Questionnaire (EBIQ)Functional outcome/QoL
General Health Questionnaire-30 (GHQ-30)Functional outcome/depression
Hamilton Depression Rating Scale (HAM-D)Depression
Mini International Neuropsychiatric InterviewDepression
Wimbledon Self-Report ScaleDepression
Beck's Depression Inventory (BDI)Depression
Patient Health Questionnaire 9-item depression scale (PHQ-9)Depression
Center for Epidemiologic Studies-Depression Scale [CES-D]Depression
Anxiety and depression scales from the Symptom Checklist-90Depression and anxiety
Hospital anxiety and depression scale (HADS)Depression and anxiety
Beck's anxiety inventory (BAI)Anxiety
36-Item Short Form Survey (SF-36)QoL
12-Item Short Form Survey (SF-12)QoL
Short-Form Six-Dimension (SF- 6D)QoL
Quality of Life after Brain Injury (QOLIBRI)QoL
Quality of Life after Brain Injury Overall Scale (QOLIBRI-OS)QoL
Quality of Life Interview (QoLI)QoL
QOLIBRI Proxy version (Q-Pro)QoL
Traumatic Brain Injury Quality of Life (TBI-QOL)QoL
World Health Organization Quality of Life-BREF (WHOQOL-BREF)QoL
World Health Organization Quality of Life 100 (WHOQOL-100)QoL
EuroQol-5D (EQ-5D)QoL
NeuroQolQoL
Sickness Impact Profile (SIP)QoL
Flanagan Quality of Life Scale (FQolS)QoL
Perceived Quality of Life Scale (PQoL)QoL
Satisfaction With Life Scale (SWLS)QoL
Life Satisfaction Questionnaire (LiSat-11)QoL
Life Satisfaction Index I-A (LSI-A)QoL
Freiburg Questionnaire of Coping with Illness (FQCI)QoL/depression
Profile of mood states (POMS)QoL/depression
Qualitative interviewsFunctional outcome/depression/dependency/nursing home admissions
Author (year)Reporting
External validity
Internal validity-bias
Internal validity - confounding (selection bias)
Power
TQuality
123456789101112131415161718192021222324252627
Akbik et al. (2019) (Akbik et al., 2019)11110100101110001111110001016Fair
Bhullar et al. (2010) (Bhullar et al., 2010)00010100011010001111110000011Poor
Brazinova et al. (2010) (Brazinova et al., 2010)11110100001110001111110000014Poor
Brousseau et al. (2017) (Brousseau et al., 2017)11110110101010000111110000014Poor
Choi et al. (2019) (Choi et al., 2019)11110110011110001111110000016Fair
Deb et al. (1998) (Deb et al., 1998)11110110101110001111110001017Fair
Erlebach et al. (2017) (Erlebach et al., 2017)11110110111010001111110001017Fair
Gorman et al. (2020) (Gorman et al., 2020)11110100011010001111110000014Poor
Gritti et al. (2019) (Gritti et al., 2019)11110110111010001111110001017Fair
Haller et al. (2017) (Haller et al., 2017)11110110101010001111110001016Fair
Hawley et al. (2017) (Hawley et al., 2017)11010110011110001111110000015Fair
Julien et al. (2017) (Julien et al., 2017)11110110011010101111110000016Fair
Khan et al. (2017) (Khan et al., 2017)11110110011110001111110000016Fair
Kinsella et al. (2014) (Kinsella et al., 2014)11110100001110001111110000014Fair
Lecours et al. (2012) (Lecours et al., 2012)11010110111010001111110000015Fair
Lilley et al. (2016) (Lilley et al., 2016)11110110111110001111110001018Fair
Miller et al. (2017) (Miller et al., 2017)11010100001010001111110000012Poor
Mosenthal et al. (2004) (Mosenthal et al., 2004)11010110111010001111110001016Fair
Mohindra et al. (2008) (Mohindra et al., 2008)00010100001010001111110000010Poor
Røe et al. (2015) (Røe et al., 2015)11111110001010001111110000015Fair
Schmidt et al. (2019) (Schmidt et al., 2019)11111110011010001111110000016Fair
Susman et al. (2002) (Susman et al., 2002)11010100011110001111110000014Poor
Thompson et al. (2012) (Thompson et al., 2012)11010100011010001111110000013Poor
Tokutomi et al. (2008) (Tokutomi et al., 2008)11010110001010001111110000013Poor
Velez et al. (2020) (Velez et al., 2020)11110110011110001111110000016Fair
Wan et al. (2016) (Wan et al., 2016)11110110001010001111110000014Poor
Won et al. (2017) (Won et al., 2017)11110110010000001111110000013Poor

1-27 refer to questions 1–27 of the Downs and Blacks scale (Downs and Black, 1998); T=total score.

  62 in total

1.  Significant increase in acute subdural hematoma in octo- and nonagenarians: surgical treatment, functional outcome, and predictors in this patient cohort.

Authors:  Sae-Yeon Won; Daniel Dubinski; Nina Brawanski; Adam Strzelczyk; Volker Seifert; Thomas M Freiman; Juergen Konczalla
Journal:  Neurosurg Focus       Date:  2017-11       Impact factor: 4.047

2.  A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity.

Authors:  J Ware; M Kosinski; S D Keller
Journal:  Med Care       Date:  1996-03       Impact factor: 2.983

3.  Traumatic brain injury in the elderly: A level 1 trauma centre study.

Authors:  Elaine de Guise; Joanne LeBlanc; Jehane Dagher; Simon Tinawi; Julie Lamoureux; Judith Marcoux; Mohammed Maleki; Mitra Feyz
Journal:  Brain Inj       Date:  2015-01-27       Impact factor: 2.311

4.  Meta-analysis in clinical trials.

Authors:  R DerSimonian; N Laird
Journal:  Control Clin Trials       Date:  1986-09

5.  Assessment of outcome after severe brain damage.

Authors:  B Jennett; M Bond
Journal:  Lancet       Date:  1975-03-01       Impact factor: 79.321

6.  Higher age is a major driver of in-hospital adverse events independent of comorbid diseases among patients with isolated mild traumatic brain injury.

Authors:  Barbara R Schmidt; Rudolf M Moos; Dilek Könü-Leblebicioglu; Heike A Bischoff-Ferrari; Hans-Peter Simmen; Hans-Christoph Pape; Valentin Neuhaus
Journal:  Eur J Trauma Emerg Surg       Date:  2018-10-15       Impact factor: 3.693

7.  Geriatric Traumatic Brain Injury: Epidemiology, Outcomes, Knowledge Gaps, and Future Directions.

Authors:  Raquel C Gardner; Kristen Dams-O'Connor; Molly Rose Morrissey; Geoffrey T Manley
Journal:  J Neurotrauma       Date:  2018-02-15       Impact factor: 5.269

8.  Intensity of treatment, end-of-life care, and mortality for older patients with severe traumatic brain injury.

Authors:  Elizabeth J Lilley; Katherine J Williams; Eric B Schneider; Khaled Hammouda; Ali Salim; Adil H Haider; Zara Cooper
Journal:  J Trauma Acute Care Surg       Date:  2016-06       Impact factor: 3.313

9.  Neuropsychiatric sequelae one year after a minor head injury.

Authors:  S Deb; I Lyons; C Koutzoukis
Journal:  J Neurol Neurosurg Psychiatry       Date:  1998-12       Impact factor: 10.154

10.  Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

Authors:  Ewout W Steyerberg; Eveline Wiegers; Charlie Sewalt; Andras Buki; Giuseppe Citerio; Véronique De Keyser; Ari Ercole; Kevin Kunzmann; Linda Lanyon; Fiona Lecky; Hester Lingsma; Geoffrey Manley; David Nelson; Wilco Peul; Nino Stocchetti; Nicole von Steinbüchel; Thijs Vande Vyvere; Jan Verheyden; Lindsay Wilson; Andrew I R Maas; David K Menon
Journal:  Lancet Neurol       Date:  2019-10       Impact factor: 44.182

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