Clinimetrics and functional outcome one year after traumatic brain injury

This thesis is based on the findings of the FuPro-TBI (Functional Prognosis in Traumatic Brain Injury) study, which was part of the national FuPro research programme which investigated the functional prognosis of four neurological disorders: multiple sclerosis (MS), stroke, amyotrofic lateral sclerosis (ALS), and TBI. Frequently used measurement instruments were tested at different moments on their reliability and sensitivity to change. At the moment of discharge from hospital a reliable minimum set is the FIM, the FAM, and the Coop. At follow-up the data set can be extended with the NRS, the FAI, and the SIP-68 which are most sensitive to change, thereby covering all relevant domains of functioning and participation after TBI. A high level of agreement was found between patient and proxy on rating the patient’s functioning, and quality of life. Unlike results from earlier reports, in the present study no underestimation or overestimation of the patient’s limitations by the proxies was found. Few rehabilitation studies include patients from acute care hospitals. In this study 46% of the patients was discharged home and would not be taken into account in the usual prognostic studies on TBI in rehabilitation medicine. The risk of being admitted to an institution was significantly higher only for those with severe TBI [adjusted odds ratio (OR) = 14], and lowered cognitive status at the time of being discharged from hospital [adjusted OR = 12]. Our results show that patients with a caregiver with a preference for a passive coping style are more restricted in participation than patients with a caregiver with another preference for coping. One year post injury, 13% of the patients reported problems in physical functioning, 35% in cognitive functioning, and 26% in their emotional functioning. In addition, 76% of the patients were limited in psychosocial activities, 72% experienced work restrictions, and 91% of all patients reported a reduced QoL. Being a woman, having sustained a moderate TBI, and having a low physical or a low cognitive status at discharge from hospital are important predictor variables in poor functional prognosis and QoL one year after TBI

Differential item functioning of the Functional Independence Measure in higher performing neurological patients

OBJECTIVE: When comparing outcomes of the Functional Independence Measure (FIM ) between patient groups, item characteristics of the FIM should be consistent across groups. The purpose of this study was to compare item difficulty of the FIM in 3 patient groups with neurological disorders. SUBJECTS: Patients with stroke (n=295), multiple sclerosis (n=150), and traumatic brain injury (n=88). METHODS: FIM scores were administered in each group. The FIM consists of a motor domain (13 items) and a cognitive domain (5 items). Rasch rating scale analysis was performed to investigate differences in item difficulty (differential item functioning) between groups. RESULTS: Answering categories of the FIM items were reduced to 3 (from the original 7) because of disordered thresholds and low answering frequencies. Two items of the motor domain ("bladder" and "bowel") did not fit the Rasch model. For 7 out of the 11 fitting motor items, item difficulties were different between groups (i.e. showed differential item functioning). All cognitive items fitted the Rasch model, and 4 out of 5 cognitive items showed differential item functioning. CONCLUSION: Differential item functioning is present in several items of both the motor and cognitive domain of the FIM. Adjustments for differential item functioning may be required when FIMdata will be compared between groups or will be used in a pooled data analysi

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

The Psychological Inflexibility in Pain Scale (PIPS): Exploration of psychometric properties in a heterogeneous chronic pain sample

Psychological flexibility receives increasing attention as the overarching process in Acceptance and Commitment Therapy (ACT). This study investigates the psychometric properties of the Psychological Inflexibility in Pain Scale (PIPS), measuring “avoidance” and “cognitive fusion” with pain, in a heterogeneous clinical sample of 428 chronic pain patients from four rehabilitation centers. Furthermore, the relationship between the PIPS and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ) as a theoretically related measure within ACT is explored. Confirmatory factor analyses replicated acceptable/good model fit and internal consistencies. In a subsample from two rehabilitation centers (n = 237), the PIPS showed moderate to high relationships with aspects of mindfulness, pain interference in daily life, pain disability and mental health, and small relationships with pain intensity and physical functioning. The avoidance subscale explained additional variance in outcome variables beyond the FFMQ, ranging from 4.5 to 15.8%. Outcomes support the psychometric properties of the PIPS in a heterogeneous chronic pain sample. The PIPS and FFMQ measure slightly overlapping, but distinct constructs, and can be used complementary to assess a broad range of processes within ACT. Potential problems with the cognitive fusion subscale are acknowledged for future researc

Measuring avoidance of pain: validation of the Acceptance and Action Questionnaire II-pain version

Psychometric research on widely used questionnaires aimed at measuring experiential avoidance of chronic pain has led to inconclusive results. To test the structural validity, internal consistency, and construct validity of a recently developed short questionnaire: the Acceptance and Action Questionnaire II-pain version (AAQ-II-P). Cross-sectional validation study among 388 adult patients with chronic nonspecific musculoskeletal pain admitted for multidisciplinary pain rehabilitation in four tertiary rehabilitation centers in the Netherlands. Cronbach’s α was calculated to analyze internal consistency. Principal component analysis was performed to analyze factor structure. Construct validity was analyzed by examining the association between acceptance of pain and measures of psychological flexibility (two scales and sum), pain catastrophizing (three scales and sum), and mental and physical functioning. Interpretation was based on a-priori defined hypotheses. The compound of the seven items of the AAQ-II-P shows a Cronbach’s α of 0.87. The single component explained 56.2% of the total variance. Correlations ranged from r=−0.21 to 0.73. Two of the predefined hypotheses were rejected and seven were not rejected. The AAQ-II-P measures a single component and has good internal consistency, and construct validity is not rejected. Thus, the construct validity of the AAQ-II-P sum scores as indicator of experiential avoidance of pain was supported