Frailty and Other Factors Associated With Early Outcomes in Middle-to Older Age Trauma Patients: A Prospective Cohort Study.

OBJECTIVES: To prospectively investigate associations of frailty and other predictor variables with functional recovery and health outcomes in middle-aged and older patients with trauma. DESIGN: Single-center prospective cohort study. SETTING: Emergency department of Wan Fang Hospital in Taiwan. PARTICIPANTS: Trauma patients aged 45 and older. MEASUREMENTS: Frailty was assessed with the Clinical Frailty Scale (CFS). Injury mechanisms, pre-existing diseases, and fracture locations were recorded at baseline. The primary outcome was functional recovery assessed using the Barthel Index (BI). Secondary outcomes were new care needs, unscheduled return visits, and falls 3 months postinjury. RESULTS: A total of 588 participants were included in the final analysis. For every one-point increase in the CFS, the multivariable-adjusted odds ratio (OR, 95% confidence interval [CI]) of failure to retain the preinjury BI was 1.34 (1.16-1.55); associations were consistent across levels of age and injury severities. Significant joint associations of frailty and age with poor functional recovery were observed. CFS was also associated with new care needs (OR for every one-point increase, 1.36, 95% CI, 1.17-1.58), unscheduled return visits (OR 1.26, 95% CI, 1.04-1.51), and falls (OR 1.23, 95% CI, 1.01-1.51). Other variables associated with failure to retain preinjury BI included road traffic accident and presence of hip fracture. CONCLUSION: Frailty was significantly associated with poor functional and health outcomes regardless of injury severity in middle-aged and older patients with trauma. Injury mechanisms and fracture locations were also significant predictors of functional recovery postinjury.

Increased short- and long-term risk of sleep disorders in people with traumatic brain injury.

This study aims to evaluate the relationship between traumatic brain injury (TBI) and sleep disorders (SDs). We first initiated a questionnaire-based clinical survey to assess sleep problems in the early stage after a TBI, followed by a population-based cohort study to evaluate the long-term risk of SDs in TBI patients. For short-term clinical survey, mild (m)TBI patients and healthy controls were recruited to evaluate the sleep quality and daytime sleepiness using the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) within two weeks after a TBI. For long-term observation, a 5-year nationwide population-based cohort study that utilized a large administrative database was conducted. In the short-term survey, 236 mTBI patients and 223 controls were analyzed. Total scores of the PSQI and ESS were significantly higher in mTBI patients than in the controls. In the long-term cohort study, 6932 TBI cases and 34,660 matched controls were included. TBI cases had a 1.36-fold greater risk of SDs compared to the non-TBI controls during the 5-year follow-up period. Results showed that patients with TBI had a significantly higher risk of SDs than did controls both in the early stage and during a 5-year follow-up period.

Effect of motorcycle helmet types on head injuries: evidence from eight level-I trauma centres in Taiwan.

BACKGROUND: Motorcycle full-coverage helmet use may reduce fatalities and head injuries. METHODS: This retrospective cohort study extracted injury data from eight level-I trauma centres in Taiwan and performed a questionnaire survey to investigate injuries sustained by motorcyclists for the period between January 2015 and June 2017. RESULTS: As many as 725 patients participated in the questionnaire survey and reported their helmet types or phone use during crashes. The results of multivariate logistic models demonstrated that nonstandard helmet (half or open-face helmet) use was associated with an increased risk of head injuries and more severe injuries (injury severity score ≥ 8). Drunk riding and phone use appeared to be two important risk factors for head injuries and increased injury severity. Anaemia was also found to be a determinant of head injuries." CONCLUSIONS: Compared to full-coverage helmets, nonstandard provide less protection against head injuries and increased injury severity among motorcyclists.

Case study: international healthcare service quality, building a model for cultivating cultural sensitivity.

QUALITY PROBLEM OR ISSUE: In the context of medical tourism, cultural differences and language barriers are unneglectable factors, which compromise the shared decision-making between doctor and patients. INITIAL ASSESSMENT: This study constructs a cultural sensitivity cultivation (CSC) model that could be used to train medical professionals in the sector of medical tourism. CHOICE OF SOLUTION: Since 2016, there have been explorations in new strategies to offer better services. A critical step added is to include clients' perspectives in the re-examining process as a way to cultivate cultural sensitivity among the service providers. This practice expands to the sector of medical tourism. In our case study, we are able to conclude a new model that could yield quality international healthcare services. IMPLEMENTATION: The steps of our CSC model include (i) 'Promote Awareness' for shifting mindset, (ii) 'Share Scenarios' for developing empathy and compassion, (iii) 'Review Process' for collecting detail feedback, (iv) 'Identify Gaps' for targeting areas for improvement and (v) 'Improve Systems,' for changing standard operation procedures (SOPs) based on the strategies through Assmann's theory with a cultural-anthropological approach. EVALUATION: After Kuang Tien General Hospital (KTGH) implemented the new model for 1 year, the number of international patients has increased by 64%. More research could be done in the future to cover all the important aspects of providing international medical services and could apply the CSC model to different healthcare settings. LESSONS LEARNED: To optimize the shared decision-making between the doctor and medical traveler patients, healthcare providers should not only overcome language and cultural barriers but also should avoid unnecessary gestures in terms of status respect. Inviting patients to be co-investigator for quality improvement is a viable solution.

The functional roles of IGF-1 variants in the susceptibility and clinical outcomes of mild traumatic brain injury.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) is an important pleiotropic hormone that exerts neuroprotective and neuroreparative effects after a brain injury. However, the roles of IGF-1 variants in mild traumatic brain injury (mTBI) are not yet fully understood. This study attempted to elucidate the effects of IGF-1 variants on the risk and neuropsychiatric outcomes of mTBI. METHODS: Based on 176 recruited mTBI patients and 1517 control subjects from the Taiwan Biobank project, we first compared the genotypic distributions of IGF-1 variants between the two groups. Then, we analyzed associations of IGF-1 variants with neuropsychiatric symptoms after mTBI, including anxiety, depression, dizziness, and sleep disturbances. Functional annotation of IGF-1 variants was also performed through bioinformatics databases. RESULTS: The minor allele of rs7136446 was over-represented in mTBI patients compared to community-based control subjects. Patients carrying minor alleles of rs7136446 and rs972936 showed more dizziness and multiple neuropsychiatric symptoms after brain injury. CONCLUSIONS: IGF-1 variants were associated with the risk and neuropsychiatric symptoms of mTBI. The findings highlight the important role of IGF-1 in the susceptibility and clinical outcomes of mTBI.

Effects of helmet nonuse and seating position on patterns and severity of injuries in child motorcycle passengers.

BACKGROUND: A prospective study was conducted to investigate the effects of helmet nonuse and seating position on patterns and severity of motorcycle injuries among child passengers in Taiwan. METHODS: In total, 305 child passengers aged ≤14 years who visited the emergency departments of three teaching hospitals following a motorcycle crash were recruited. Children's injury data were collected from medical records, and their riding behaviors along with operators' demographics were sourced from telephone interviews. Parental responses over the telephone about children's riding behaviors were checked by roadside observations. RESULTS: Results of the multivariable logistic regression analysis revealed that compared to child passengers aged ≥7 years, those aged ≤3 (odds ratio (OR), 2.88; 95% confidence interval (CI), 1.37~6.06) and 4~6 years (OR, 2.93; 95% CI, 1.50~5.70) were significantly more likely to have sustained a head/face injury, while those aged 4~6 years (OR, 2.76; 95% CI, 1.01~7.55) were significantly more likely to have sustained a severe injury. Compared to child passengers who were wearing a full-coverage helmet, those who were not wearing a helmet were significantly more likely to have sustained a head/face injury (OR, 3.12; 95% CI, 1.02~9.52) and a severe injury (OR, 3.02; 95% CI, 1.19~7.62). Children seated in front of the operator were significantly more likely to have experienced a head/face injury (OR, 2.22; 95% CI, 1.25~3.94) than those seated behind the operator. For each increment in the riding speed of 1 km/h, the odds of a severe injury to child passengers increased by 5% (OR, 1.05; 95% CI, 1.01~1.09). CONCLUSIONS: For the safety of child motorcycle passengers, laws on a minimum age restriction, helmet use, an adequate seating position, and riding speed need to be enacted and comprehensively enforced.

Improving the timeliness and accuracy of injury severity data in road traffic accidents in an emerging economy setting.

Road traffic injuries (RTIs) are among the leading causes of injury and fatality worldwide. RTI casualties are continually increasing in Taiwan; however, because of a lack of an advanced method for classifying RTI severity data, as well as the fragmentation of data sources, road traffic safety and health agencies encounter difficulties in analyzing RTIs and their burden on the healthcare system and national resources. These difficulties lead to blind spots during policy-making for RTI prevention and control. After compiling classifications applied in various countries, we summarized data sources for RTI severity in Taiwan, through which we identified data fragmentation. Accordingly, we proposed a practical classification for RTI severity, as well as a feasible model for collecting and integrating these data nationwide. This model can provide timely relevant data recorded by medical professionals and is valuable to healthcare providers. The proposed model's pros and cons are also compared to those of other current models.

Effect of Age on Working Memory Performance and Cerebral Activation after Mild Traumatic Brain Injury: A Functional MR Imaging Study.

PURPOSE: To evaluate the age effect on working memory (WM) performance and functional activation after mild traumatic brain injury (MTBI). MATERIALS AND METHODS: This study was approved by the local research ethics committee. All participants provided written informed consent. N-back WM cerebral activation was assessed with functional magnetic resonance (MR) imaging in 13 younger (mean age, 26.2 years ± 2.9; range, 21-30 years) and 13 older (mean age, 57.8 years ± 6.6; range, 51-68 years) patients with MTBI and 26 age- and sex-matched control subjects. Two functional MR images were obtained within 1 month after injury and 6 weeks after the initial study. Group comparison and regression analysis were performed among postconcussion symptoms, neuropsychologic tests, and WM activity in both groups. RESULTS: In younger patients, initial hyperactivation was seen in the right precuneus and right inferior parietal gyrus (P = .047 and P = .025, respectively) in two-back greater than one-back conditions compared with younger control subjects, whereas in older patients, hypoactivation was seen in the right precuneus and right inferior frontal gyrus (P = .013 and P =.019, respectively) compared with older control subjects. Increased WM activity was associated with increased postconcussion symptoms in the right precuneus (r = 0.57; P = .026) and right inferior frontal gyrus (r = 0.60; P = .019) and poor WM performance in the right precuneus (r = -0.55; P = .027) in younger patients at initial studies but not in older patients. At follow-up examinations, partial recovery of activation pattern and decreased postconcussion symptoms (P = .04) were observed in younger patients but not in older patients. CONCLUSION: The different manifestations of postconcussion symptoms at functional MR imaging between younger and older patients confirmed the important role of age in the activation, modulation, and allocation of WM processing resources after MTBI. These findings also supported that younger patients have better neural plasticity and clinical recovery than do older patients.

Association of traumatic brain injury in childhood and attention-deficit/hyperactivity disorder: a population-based study.

BACKGROUND: We evaluated the risk of attention-deficit hyperactivity disorder (ADHD) following childhood traumatic brain injury (TBI). METHODS: Using Taiwan's National Health Insurance Research Database, we included 10,416 newly diagnosed TBI children (aged ≤12 y) between 2001 and 2002 and 41,664 children without TBI, who were frequency matched by sex, age, and year of the index medical service with each TBI child, as controls. Children who had been diagnosed with ADHD prior to their medical service index were excluded. Each individual was followed for 9 y to identify ADHD diagnosis. We also compared the ADHD risk in children who were treated for fractures but not TBI as sensitivity analysis. RESULTS: During the 9-y follow-up period, children with TBI had a higher ADHD risk (adjusted hazard ratio (AHR) = 1.32, 95% confidence interval (CI) = 1.19, 1.45) than did those without TBI. Furthermore, children with mild and severe TBI had higher AHRs for ADHD than did those without TBI (AHR = 1.30; 95% CI = 1.10, 1.53; and AHR = 1.37; 95% CI = 1.22, 1.55). However, no significant association was observed between fractures and ADHD. CONCLUSION: TBI in childhood is associated with a greater likelihood of developing ADHD.

Sex Differences in Working Memory after Mild Traumatic Brain Injury: A Functional MR Imaging Study.

PURPOSE: To evaluate sex differences in mild traumatic brain injury (MTBI) with working memory functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: Research ethics committee approval and patient written informed consent were obtained. Working memory brain activation patterns were assessed with functional MR imaging in 30 patients (15 consecutive men and 15 consecutive women) with MTBI and 30 control subjects (15 consecutive men and 15 consecutive women). Two imaging studies were performed in patients: the initial study, which was performed within 1 month after the injury, and a follow-up study, which was performed 6 weeks after the first study. For each participant, digit span and continuous performance testing were performed before functional MR imaging. Clinical data were analyzed by using Kruskal-Wallis, Mann-Whitney U, Wilcoxon signed rank, and Fisher exact tests. Within- and between-group differences of functional MR imaging data were analyzed with one- and two-sample t tests, respectively. RESULTS: Among female participants, the total digit span score was lower in the MTBI group than in the control group (P = .044). In initial working memory functional MR imaging studies, hyperactivation was found in the male MTBI group and hypoactivation was found in the female MTBI group compared with control male and female groups, respectively. At the 6-week follow-up study, the female MTBI group showed persistent hypoactivation, whereas the male MTBI group showed a regression of hyperactivation at visual comparison of activation maps. The male MTBI group was also found to have a higher initial ß value than the male control group (P = .040), and there was no significant difference between the male MTBI group and the male control group (P = .221) at follow-up evaluation, which was comparable to findings on activation maps. In the female MTBI group, average ß values at both initial and follow-up studies were lower compared with those in the female control group but were not statistically significant (P = .663 and P = .191, respectively). CONCLUSION: Female patients with MTBI had lower digit span scores than did female control subjects, and functional MR imaging depicted sex differences in working memory functional activation; hypoactivation with nonrecovery of activation change at follow-up studies may suggest a worse working memory outcome in female patients with MTBI.

Balance function and sensory integration after mild traumatic brain injury.

OBJECTIVE: This study examined the disparities in balance functions and sensory integration in patients with mild traumatic brain injuries (mTBIs) and healthy controls. PARTICIPANTS: One hundred and seven patients with mTBI and 107 age- and sex-matched controls were recruaited for this study. PRIMARY MEASURES: Symptoms of dizziness, balance functions and the ability to perform daily activities were assessed using the dizziness handicap inventory (DHI). This study also performed the postural-stability test and a modified clinical test of sensory integration by using the Biodex Stability System (BBS). RESULTS: DHI scores (functional, emotional, physical and total self-reported scores) were substantially increased in patients following an mTBI compared with the scores of the controls (p < 0.000). The postural-stability test indices (anterior-posterior) (p = 0.045) and the sensory-integration test index (eyes-open-firm-surface index) (p = 0.006) were substantially lower in patients with mTBI than in the controls. However, indices of two other postural-stability test indices (overall and medial-lateral) and three other sensory-integration tests indices (eyes-closed-firm-surface, eyes-open-foam-surface and eyes-closed-foam-surface) measured for the mTBI group did not differ from those of the control group. CONCLUSION: Activities of daily living, balance in postural stability and sensory integration were strongly impaired in patients with mTBI.

A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis.

PURPOSE: Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease. METHODS: We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family. RESULTS: We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells. CONCLUSION: Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis.Genet Med 16 10, 787-792.

Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling.

Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown. We isolated the zebrafish ptpro gene and found that its transcripts are primarily expressed in the embryonic and adult central nervous system. Depletion of zebrafish embryonic Ptpro by antisense morpholino oligonucleotide knockdown resulted in prominent defects in the forebrain and cerebellum, and the injected larvae died on the 4th day post-fertilization (dpf). We further investigated the function of ptpro in cerebellar development and found that the expression of ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro morphants. Further analyses demonstrated that cerebellar defects of ptpro morphants were partially rescued by inhibiting Fgf signaling. Moreover, Ptpro physically interacted with the Fgf receptor 1a (Fgfr1a) and dephosphorylated Fgfr1a in a dose-dependant manner. Therefore, our findings demonstrate that Ptpro activity is required for patterning the zebrafish embryonic brain. Specifically, Ptpro regulates cerebellar formation during zebrafish development through modulating Fgf signaling.

Validation of the quality of life after brain injury in Chinese persons with traumatic brain injury in Taiwan.

OBJECTIVE: To determine the psychometric properties of the Quality of Life After Brain Injury (QOLIBRI) in Chinese persons with traumatic brain injury (TBI) in Taiwan. PARTICIPANTS: Three hundred one patients with TBI were interviewed face-to-face at baseline; of these, 132 completed a follow-up assessment 1 year later. SETTINGS: Neurosurgery clinics of 6 teaching hospitals in northern Taiwan. MEASURE: The 37-item QOLIBRI, including 6 domains of Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, and Physical Problems. RESULTS: A small percentage (<1%) of responses were missing, except the Sex Life item under the Social domain (5.9%). The QOLIBRI achieved adequate percentages for the floor value (0%-4%), ceiling value (1%-3.3%), internal consistency (0.79-0.95), and test-retest reliability (0.81-0.89). For construct validity, correlation coefficients (rs) for the QOLIBRI domains and selected clinical measures conceptually related to that domain were all 0.4 or more, except rs for QOLIBRI Cognition and Mini-Mental State Examination scores. A principal components analysis found that one item (Loneliness) of the Emotions domain did not converge with its corresponding domain of the original QOLIBRI (loading score <0.4). Effect sizes of responsiveness to changes in the Glasgow Outcome Scale-Extended over the 1-year period were clinically meaningful for all the QOLIBRI domains except the Emotions domain. CONCLUSION: With modifications to the Emotions domain, the QOLIBRI would be suitable for use with Chinese people in Taiwan who have TBI.

Risk and mortality of traumatic brain injury in stroke patients: two nationwide cohort studies.

OBJECTIVE: Patients with stroke had higher incidence of falls and hip fractures. However, the risk of traumatic brain injury (TBI) and post-TBI mortality in patients with stroke was not well defined. Our study is to investigate the risk of TBI and post-TBI mortality in patients with stroke. METHODS: Using reimbursement claims from Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 7622 patients with stroke and 30 488 participants without stroke aged 20 years and older as reference group. Data were collected on newly developed TBI after stroke with 5 to 8 years' follow-up during 2000 to 2008. Another nested cohort study including 7034 hospitalized patients with TBI was also conducted to analyze the contribution of stroke to post-TBI in-hospital mortality. RESULTS: Compared with the nonstroke cohort, the adjusted hazard ratio of TBI risk among patients with stroke was 2.80 (95% confidence interval = 2.58-3.04) during the follow-up period. Patients with stroke had higher mortality after TBI than those without stroke (10.2% vs 3.2%, P < .0001) with an adjusted relative risk (RR) of 1.46 (95% confidence interval = 1.15-1.84). Recurrent stroke (RR = 1.60), hemorrhagic stroke (RR = 1.68), high medical expenditure for stroke (RR = 1.80), epilepsy (RR = 1.79), neurosurgery (RR = 1.94), and hip fracture (RR = 2.11) were all associated with significantly higher post-TBI mortality among patients with stroke. CONCLUSIONS: Patients with stroke have an increased risk of TBI and in-hospital mortality after TBI. Various characteristics of stroke severity were all associated with higher post-TBI mortality. Special attention is needed to prevent TBI among these populations.

Validity and reliability of the Functioning Disability Evaluation Scale-Adult Version based on the WHODAS 2.0--36 items.

BACKGROUND/PURPOSE: The disability eligibility determination system is based on the International Classification of Functioning, Disability and Health (ICF) framework in Taiwan. The Functioning Disability Evaluation Scale (FUNDES) has been developed since 2007 for assessing the status of an individual's activities and participation in the disability eligibility system. The purpose of this study was to examine the reliability and validity of the FUNDES-Adult Version (FUNDES-Adult). METHODS: During 2011-2012, a total of 5736 adults with disabilities (aged 58.4 ± 18.2 years) were randomly recruited for a national population-based study. These adults were assessed in person by certified professionals in the authorized hospitals. Domains 1-6 of the FUNDES-Adult addressing the performance and capability dimensions are modified from the World Health Organization Disability Assessment Schedule 2.0-36-item version, and Domain 7 (Environmental attribute) and capability and capacity dimensions of Domain 8 (Motor action) are designed based on the ICF coding system. RESULTS: The internal consistency was excellent (Cronbach's α ≥ 0.9). An exploratory factor analysis yielded a five-factor FUNDES structure with a variance of 76.1% and 76.9% and factor loadings of 0.56-0.94 and 0.55-0.94 for the performance and capability dimensions, respectively. The factor loadings for the second-order confirmatory factor analysis for the performance and capability dimensions were from 0.81 to 0.89. In Domains 1-6 and 8, the ceiling effects were from 9% to 36%, and the floor effects were from 5% to 45%. CONCLUSION: FUNDES-Adult has acceptable reliability and validity and can be used to measure activities and participation for people with disabilities.

Risk of epilepsy after traumatic brain injury: a retrospective population-based cohort study.

OBJECTIVE: To investigate the associated risk of epilepsy after traumatic brain injury (TBI) in a population-based retrospective cohort study. METHODS: Using Taiwan's National Health Insurance Research Database of reimbursement claims, we conducted a retrospective cohort study of 19 336 TBI patients and 540 322 non-TBI participants aged ≥15 years as reference group. Data on newly developed epilepsy after TBI with 5-8 years' follow-up during 2000 to 2008 were collected. HRs and 95% CIs for the risk of epilepsy associated with TBI were analysed with multivariate Cox proportional hazards regressions. RESULTS: Compared with the non-TBI cohort, the adjusted HRs of developing epilepsy among TBI patients with skull fracture, severe or mild brain injury were 10.6 (95% CI 7.14 to 15.8), 5.05 (95% CI 4.40 to 5.79) and 3.02 (95% CI 2.42 to 3.77), respectively. During follow-up, men exhibited higher risks of post-TBI epilepsy. Patients who had mixed types of cerebral haemorrhage were at the highest risk of epilepsy compared with the non-TBI cohort (HR 7.83, 95% CI 4.69 to 13.0). The risk of post-TBI epilepsy was highest within the first year after TBI (HR 38.2, 95% CI 21.7 to 67.0). CONCLUSIONS: The risk of epilepsy after TBI varied by patient gender, age, latent interval and complexity of TBI. Integrated care for early identification and treatment of post-trauma epilepsy were crucial for TBI patients.