Search

Contains fulltext : 235370.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. MATERIALS AND METHODS: Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MD(z)). Through linear regression, we evaluated the relation between microbleed concentration and MD(z) in predefined structures. RESULTS: In the cerebral hemispheres, MD(z) at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5-69.3], P = .017; right: B = 26.3 [95% CI 5.7-47.0], P = .014). No such relation was demonstrated in the central brain. MD(z) in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8-75.2], P < .000). MD(z) in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9-47.5], P = .023). CONCLUSIONS: SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a “small-to-medium” sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.

Traumatic brain injury is a multifaceted condition that encompasses a spectrum of injuries: contusions, axonal injuries in specific brain regions, edema, and hemorrhage. Brain injury determines a broad clinical and disability spectrum due to the implication of various cellular pathways, genetic phenotypes, and environmental factors. It is challenging to predict patient outcomes, to appropriately evaluate the patients, to determine a suitable treatment strategy and rehabilitation program, and to communicate with patient relatives. Biomarkers detected from body fluids are potential evaluation tools for traumatic brain injury patients. These may serve as internal indicators of cerebral damage, delivering valuable information about the dynamic cellular, biochemical, and molecular environments. The diagnostic and prognostic value of biomarkers tested both in animal models of traumatic brain injury is still under question, despite a considerable scientific literature. Recent publications emphasize that a more realistic approach involves combining multiple types of biomarkers with other investigative tools (imaging, outcome scales, and genetic polymorphisms). Additionally, there is increasing interest in the use of biomarkers as tools for treatment monitoring and as surrogate outcome variables to facilitate the design of distinct randomized controlled trials. This review highlights the latest available evidence regarding biomarkers in adults after traumatic brain injury and discusses new approaches in the evaluation of this patient group.

Serum concentrations of free thiols (key components of the extracellular antioxidant machinery) reflect the overall redox status of the human body. The objective of this exploratory study was to determine the concentrations of serum free thiols in the acute phase after traumatic brain injury (TBI) and their association with long-term outcome. In this observational cohort study, patients with TBI of various severity were included from a biobank of prospectively enrolled TBI patients. Further eligibility criteria included an available blood sample and head computed tomography data, obtained within 24 h of injury, as well as a functional outcome assessment (Glasgow Outcome Scale Extended (GOSE)) at 6 months post-injury. Serum free thiol concentrations were markedly lower in patients with TBI (n = 77) compared to healthy controls (n = 55) (mean ± standard deviation; 210.3 ± 63.3 vs. 301.8 ± 23.9 μM, P P = 0.016), suggesting that patients with good recovery experience less oxidative stress in the acute phase after TBI or have better redox function. Acute TBI is accompanied by a markedly lower concentration of serum free thiols compared to healthy controls indicating that serum free thiols may be a novel biomarker of TBI. Future studies are warranted to validate our findings and explore the clinical applicability and prognostic capability of this candidate-biomarker.

The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a “small-to-medium”–sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.

Rapid risk-stratification of patients with acute traumatic brain injury (TBI) would inform management decisions and prognostication. The objective of this serum biomarker study (Biomarkers of Injury and Outcome [BIO]-Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment [ProTECT]) was to test the hypothesis that serum biomarkers of structural brain injury, measured at a single, very early time-point, add value beyond relevant clinical covariates when predicting unfavorable outcome 6 months after moderate-to-severe acute TBI. BIO-ProTECT utilized prospectively collected samples obtained from subjects with moderate-to-severe TBI enrolled in the ProTECT III clinical trial of progesterone. Serum samples were obtained within 4 h after injury. Glial fibrillary acidic protein (GFAP), S100B, αII-spectrin breakdown product of molecular weight 150 (SBDP150), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) were measured. The association between log-transformed biomarker levels and poor outcome, defined by a Glasgow Outcome Scale-Extended (GOS-E) score of 1–4 at 6 months post-injury, were estimated via logistic regression. Prognostic models and a biomarker risk score were developed using bootstrapping techniques. Of 882 ProTECT III subjects, samples were available for 566. Each biomarker was associated with 6-month GOS-E (p

Introduction In order to augment the certainty of the radiological interpretation of “possible microbleeds” after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. Methods Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. Results Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. Conclusions Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.

Contains fulltext : 219917.pdf (Publisher’s version ) (Open Access)

To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury.The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure.In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pOur trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.

Contains fulltext : 203532.pdf (Publisher’s version ) (Closed access) In this study we investigated the effects of seeking versus avoiding proximity to mother on children's emotional recovery from a stressor. Sixty children 9-12 years underwent a moodinduction procedure and were randomly assigned to seek proximity from or avoid an image of their mothers. The effect of this manipulation on children's self-reported negative emotions, skin conductance and heart rate variability (respiratory sinus arhythmia) was assessed. Higher levels of attachment anxiety were linked to more self-reported sadness when children had to avoid mother, but no evidence for such an effect was found on a physiological level. For avoidant attachment, a similar pattern of results emerged, but both for self-reported sadness and skin conductance. 19 p.

Background: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of CT variables. The objectives of this study were to train research assistants (RAs) to rate CDEs and then to evaluate their performance. The aim was to assess inter-rater reliability (IRR) of CDEs between trained RAs and a neurologist and to evaluate applicability of CDEs in acute and sub-acute TBI to test the feasibility of using CDE CT ratings in future trials and ultimately in clinical practice. The second aim was to confirm that the ratings of CDEs reflect pathophysiological events after TBI.Methods and results: First, a manual was developed for application of the CDEs, which was used to rate brain CTs (n = 100). An excellent agreement was found in combined kappas between RAs on admission and on 24-hour follow-up CTs (Iota = 0.803 and 0.787, respectively). Good IRR (kappa > 0.61) was shown for six CDEs on admissions and for seven CDEs on follow-up CTs. Low IRR (kappa

Background The vegetative state, also known as the unresponsive wakefulness syndrome, is one of the worst possible outcomes of acquired brain injury and confronts rehabilitation specialists with various challenges. Emergence to (minimal) consciousness is classically considered unlikely beyond 3–6 months after non-traumatic or 12 months after traumatic etiologies. A growing body of evidence suggests that these timeframes are too narrow, but evidence regarding chances of recovery is still limited. Objective To identify the moment of recovery of consciousness in documented cases of late emergence from a vegetative state. Methods Four cases of apparent late recovery of consciousness, identified within a prospective cohort study, were studied in-depth by analyzing medical, paramedical and nursing files and interviewing the patients’ families about their account of the process of recovery. Results All patients were found to have shown signs of consciousness well within the expected time frame (5 weeks–2 months post-ictus). These behaviors, however, went unnoticed or were misinterpreted, leading to a diagnostic delay of several months to over 5 years. Absence of appropriate diagnostics, the use of erroneous terminology, sedative medication but also patient-related factors such as hydrocephalus, language barriers and performance fluctuations are hypothesized to have contributed to the delay. Conclusions Delayed recognition of signs of consciousness in patients in a vegetative state may not only lead to suboptimal clinical care, but also to distorted prognostic figures. Discriminating late recovery from the delayed discovery of consciousness, therefore, is vital to both clinical practice and science.

Maryse C Cnossen,1 Thomas A van Essen,2,3 Iris E Ceyisakar,1 Suzanne Polinder,1 Teuntje M Andriessen,4 Joukje van der Naalt,5 Iain Haitsma,6 Janneke Horn,7 Gaby Franschman,8 Pieter E Vos,9 Wilco C Peul,2,3 David K Menon,10 Andrew IR Maas,11 Ewout W Steyerberg,1,12 Hester F Lingsma1 1Center for Medical Decision Making, Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; 2Neurosurgical Cooperative Holland, Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Neurosurgery, Haaglanden Medical Center, The Hague, the Netherlands; 4Department of Psychology, RIVAS Healthcare Group, Gorinchem, the Netherlands; 5Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands; 6Department of Neurosurgery, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; 7Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 8Department of Anesthesiology, VU University Medical Center Amsterdam, Amsterdam, the Netherlands; 9Department of Neurology, Slingeland Hospital, Doetinchem, the Netherlands; 10Division of Anaesthesia, University of Cambridge/Addenbrooke’s Hospital, Cambridge, UK; 11Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium; 12Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands Introduction: Observational studies of interventions are at risk for confounding by indication. The objective of the current study was to define the circumstances for the validity of methods to adjust for confounding by indication in observational studies. Patients and methods: We performed post hoc analyses of data prospectively collected from three European and North American traumatic brain injury studies including 1,725 patients. The effects of three interventions (intracranial pressure [ICP] monitoring, intracranial operation and primary referral) were estimated in a proportional odds regression model with the Glasgow Outcome Scale as ordinal outcome variable. Three analytical methods were compared: classical covariate adjustment, propensity score matching and instrumental variable (IV) analysis in which the percentage exposed to an intervention in each hospital was added as an independent variable, together with a random intercept for each hospital. In addition, a simulation study was performed in which the effect of a hypothetical beneficial intervention (OR 1.65) was simulated for scenarios with and without unmeasured confounders. Results: For all three interventions, covariate adjustment and propensity score matching resulted in negative estimates of the treatment effect (OR ranging from 0.80 to 0.92), whereas the IV approach indicated that both ICP monitoring and intracranial operation might be beneficial (OR per 10% change 1.17, 95% CI 1.01–1.42 and 1.42, 95% CI 0.95–1.97). In our simulation study, we found that covariate adjustment and propensity score matching resulted in an invalid estimate of the treatment effect in case of unmeasured confounders (OR ranging from 0.90 to 1.03). The IV approach provided an estimate in the similar direction as the simulated effect (OR per 10% change 1.04–1.05) but was statistically inefficient. Conclusion: The effect estimation of interventions in observational studies strongly depends on the analytical method used. When unobserved confounding and practice variation are expected in observational multicenter studies, IV analysis should be considered. Keywords: confounding, observational studies, traumatic brain injury, instrumental variable analysis, comparative effectiveness research

OBJECTIVES: Various definitions for concussion have been proposed, each having its strengths and weaknesses. We reviewed and compared current definitions and identified criteria necessary for an operational definition of sports-related concussion (SRC) in preparation of the 5th Concussion Consensus Conference (Berlin, Germany). We also assessed the role of biomechanical studies in informing an operational definition of SRC.DESIGN: This is a systematic literature review.DATA SOURCES: Data sources include MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Clinical Trials and SPORT Discus (accessed 14 September 2016).ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligibility criteria were studies reporting (clinical) criteria for diagnosing SRC and studies containing SRC impact data.RESULTS: Out of 1601 articles screened, 36 studies were included (2.2%), 14 reported on criteria for SRC definitions and 22 on biomechanical aspects of concussions. Six different operational definitions focusing on clinical findings and their dynamics were identified. Biomechanical studies were obtained almost exclusively on American football players. Angular and linear head accelerations linked to clinically confirmed concussions demonstrated considerable individual variation.SUMMARY/CONCLUSIONS: SRC is a traumatic brain injury that is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces with several common features that help define its nature. Limitations identified include that the current criteria for diagnosing SRC are clinically oriented and that there is no gold/standard to assess their diagnostic properties. A future, more valid definition of SRC would better identify concussed players by demonstrating high predictive positive/negative values. Currently, the use of helmet-based systems to study the biomechanics of SRC is limited to few collision sports. New approaches need to be developed to provide objective markers for SRC.

Background Few studies examined joint attention in interactions with people with profound intellectual and multiple disabilities (PIMD), although being an important component of high-quality interaction. The purpose of this study is to describe initiating joint attention behaviour from people with PIMD and their support workers as well as the sequential relationship between initiating joint attention behaviour and attention episodes in spontaneous interactions. Method Video observations of 28 support worker–client dyads were coded using partial interval coding. Results Results show much variation across persons and dyads. Within the support worker–client dyad, there is not much joint attention but shared attention is frequently occurring. In general, people with PIMD are directing the attention of their interaction partner at low rates. The support workers are frequently directing the attention of the clients towards a topic of interest but not often through the tactile modality. The occurrence of an attention episode cannot be predicted on the basis of preceding initiating joint attention behaviour of the interaction partners. Conclusion This study presents directions for future research and implications for practice. It may increase support workers' knowledge of their own contributions, strengths and weaknesses in directing and maintaining attention within interactions with people with PIMD.

Background Behavioural observations are the most frequently used source of information about emotions of people with severe or profound intellectual disabilities but have not yet been validated against other measures of emotion. In this study we wanted to validate the behavioural observations of emotions using respiration (rib cage contribution, total breath duration, inspiratory time, expiratory time, tidal volume, mean inspiratory flow, minute ventilation) and heart rate variability. Method Twenty-seven participants were presented with four negative and four positive stimuli. During the presentation the participants' respiration and heart rate variability was measured. Each behaviour of the participant was coded as emotive or not. Results We found the hypothesised higher percentage rib cage contribution, marginal lower mean inspiratory flow and lower heart rate variability when the expressed emotions became more positive. Conclusions These results validate the use of behavioural observations to make inferences about emotions.

Although it is shown that attention plays an important role both in the onset and in the regulation of emotions in people without disabilities there is no information about how attention is related to emotions in people with severe or profound intellectual disability (ID). Therefore, in our study, we investigated the role of attention in the onset and regulation of the emotions of persons with severe or profound ID. We presented 27 participants with 4 staff-selected negative and 4 staff-selected positive stimuli. The situations were videotaped and their heart rate and attention was measured. Contrary to the expected higher attention to negative stimuli during the onset of negative emotions, we did not find differences in attention in the fourth to sixth second of stimulus presentation. However, in support of the emotion regulation theory of Gross (2008) we did find less attention to the negative stimuli than to the positive stimuli after these first 6 s of stimuli presentation. As expected from research in people without disabilities, there was also a negative relationship between the heart rate and the probability of being attentive. Our results suggest that people with severe and profound ID use attentional deployment to regulate their emotions and that, as in people without disabilities, a low heart rate is associated with attention. (C) 2012 Elsevier Ltd. All rights reserved.

The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p

Background There is growing interest in health related quality of life (HRQoL) as an outcome measure in international trials. However, there might be differences in the conceptualization of HRQoL across different socio-cultural groups. The objectives of current study were: (I) to compare HRQoL, measured with the short form (SF)-36 of Dutch and Chinese traumatic brain injury (TBI) patients 1 year after injury and; (II) to assess whether differences in SF-36 profiles could be explained by cultural differences in HRQoL conceptualization. TBI patients are of particular interest because this is an important cause of diverse impairments and disabilities in functional, physical, emotional, cognitive, and social domains that may drastically reduce HRQoL. Methods A prospective cohort study on adult TBI patients in the Netherlands (RUBICS) and a retrospective cohort study in China were used to compare HRQoL 1 year post-injury. Differences on subscales were assessed with the Mann-Whitney U-test. The internal consistency, interscale correlations, item-internal consistency and item-discriminate validity of Dutch and Chinese SF-36 profiles were examined. Confirmatory factor analysis was performed to assess whether Dutch and Chinese data fitted the SF-36 two factor-model (physical and mental construct). Results Four hundred forty seven Dutch and 173 Chinese TBI patients were included. Dutch patients obtained significantly higher scores on role limitations due to emotional problems (p

Objectives: Although guidelines have been developed to standardize care in traumatic brain injury, between-center variation in treatment approach has been frequently reported. We examined variation in treatment for traumatic brain injury by assessing factors influencing treatment and the association between treatment and patient outcome.Design: Secondary analysis of prospectively collected data. Setting: Five level I trauma centers in the Netherlands (2008-2009).Patients: Five hundred three patients with moderate or severe traumatic brain injury (Glasgow Coma Scale, 3-13).Interventions: We examined variation in seven treatment parameters: direct transfer, involvement of mobile medical team, mechanical ventilation, intracranial pressure monitoring, vasopressors, acute neurosurgical intervention, and extracranial operation.Measurements and Main Results: Data were collected on patient characteristics, treatment, and 6-month Glasgow Outcome Scale-Extended. Multivariable logistic regression models were used to assess the extent to which treatment was determined by patient characteristics. To examine whether there were between-center differences in treatment, we used unadjusted and adjusted random effect models with the seven treatment parameters as dependent variables. The influence of treatment approach in a center (defined as aggressive and non aggressive based on the frequency intracranial pressure monitoring) on outcome was assessed using multivariable random effect proportional odds regression models in those patients with an indication for intracranial pressure monitoring. Sensitivity analyses were performed to test alternative definitions of aggressiveness. Treatment was modestly related to patient characteristics (Nagelkerke R-2 range, 0.12-0.52) and varied widely among centers, even after case-mix correction. Outcome was more favorable in patients treated in aggressive centers than those treated in nonaggressive centers (OR, 1.73; 95% CI, 1.05-3.15). Sensitivity analyses, however, illustrated that the aggressiveness-outcome association was dependent on the definition used.Conclusions: The considerable between-center variation in treatment for patients with brain injury can only partly be explained by differences in patient characteristics. An aggressive treatment approach may imply better outcome although further confirmation is required. (Crit Care Med 2017; 45:660-669)

Background The measurement of subjective well-being in people with severe and profound intellectual disabilities (ID) is a difficult challenge. As they cannot self-report about their life satisfaction, because of severe communicative and cognitive limitations, behavioural observations of their emotions and moods are important in the measurement of their subjective well-being. It is, however, not known if observations of mood and emotion can be differentiated in people with severe and profound ID and if mood and emotions can give unique information about their affect. Therefore, the aim of this study is to examine the relationship between mood and emotions in people with severe and profound ID, using behavioural observations. As recommended in the literature, we investigated the frequency and intensity of the emotion separately. Method In a period of 3 weeks 27 participants with severe and profound ID were presented with four staff-selected negative and four staff-selected positive stimuli. During the presentation participants were videotaped using the observational method of Petry & Maes where each behaviour is coded on a 5-point scale, ranging from indicating a very negative emotion to indicating a very positive emotion. As a measure of mood, the staff completed the MIPQ in the beginning of the 3 weeks. Results We found a positive relationship between mood and respectively the total emotion score and the frequency of the emotion when the stimuli were positive but not when the stimuli were negative. There was no relationship between mood and the intensity of the emotion. Conclusions Our results indicate that mood and emotions can be distinguished from each other using behavioural observations. Both can give specific information about the affective life of people with severe or profound ID. Moreover, if further research could replicate the results of this study, an implication is that the direct support workers should be aware of a decline in the frequency of their clients reactions to positive stimuli as this could indicate a decline in their mood.

BACKGROUND: Several prognostic models to predict outcome in traumatic brain injury (TBI) have been developed, but few are externally validated. We aimed to validate the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models in a recent unselected patient cohort and to assess the additional prognostic value of extracranial injury. METHODS: The Prospective Observational COhort Neurotrauma (POCON) registry contains 508 patients with moderate or severe TBI, who were admitted in 2008 and 2009 to five trauma centers in the Netherlands. We predicted the probability of mortality and unfavorable outcome at 6 months after injury with the IMPACT prognostic models. We studied discrimination (area under the curve [AUC]) and calibration. We added the extracranial component of the Injury Severity Score (ISS) to the models and calculated the increase in AUC. RESULTS: The IMPACT models had an adequate discrimination in the POCON registry, with AUCs in the external validation between 0.85 and 0.90 for mortality and between 0.82 and 0.87 for unfavorable outcome. Observed outcomes agreed well with predicted outcomes. Adding extracranial injury slightly improved predictions in the overall population (unfavorable outcome: AUC increase of 0.002, p = 0.02; mortality: AUC increase of 0.000, p = 0.37) but more clearly in patients with moderate TBI (unfavorable outcome: AUC increase of 0.008, p G 0.01, mortality: AUC increase of 0.012, p = 0.02) and patients with minor computed tomographic result abnormalities (unfavorable outcome: AUC increase of 0.013, p G 0.01; mortality: AUC increase of 0.001, p =0 .08). CONCLUSION: The IMPACT models performed well in a recent series of TBI patients. We found some additional impact of extracranial injury on outcome, specifically in patients with less severe TBI or minor computed tomographic result abnormalities. ( JT rauma Acute Care Surg. 2013;74: 639Y646. Copyright * 2013 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Epidemiologic/prognostic study

Although observation largely takes into account the needs and abilities of individuals with profound intellectual and multiple disabilities, several difficulties are related to this assessment method as well. Our aim in this study was to investigate what possibilities the use of physiological measurements make available to validate alertness observations. Measurements of five physiological parameters were compared with video observations of three individuals with profound intellectual and multiple disabilities. Because our first findings are broadly in line with those of studies involving individuals in the general population, we hypothesize that physiological measurements can be used to validate alertness observations in individuals with profound intellectual and multiple disabilities. Future studies are needed to compensate for the limitations of this study and to answer ensuing questions.

van de Ven AC, Muntjewerff J-W, Netea-Maier RT, de Vegt F, Ross HA, Sweep FCGJ, Kiemeney LA, Vos PE, Buitelaar JK, Hermus ARMM, den Heijer M, Janzing JGE. Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression. Objective: The aim of this study was to investigate whether thyroid function and thyroid peroxidase antibodies (TPOAb) are associated with depression, when using both state and trait parameters of depression. Method: In 1125 participants of the Nijmegen Biomedical Study, thyroid-stimulating hormone (TSH), free thyroxine (FT(4) ), and TPOAb were measured twice. The Beck Depression Inventory (BDI), a self-reported lifetime diagnosis of depression, and the neuroticism scale of the Eysenck Personality Questionnaire Revised Short Scale (EPQ-RSS) were used to evaluate the presence of state and trait features of depression. Results: We found no association between TSH and FT(4) levels and BDI score, current depression, lifetime diagnosis of depression, and EPQ-RSS neuroticism score. Subjects with TPOAb had higher EPQ-RSS neuroticism scores in comparison with subjects without TPOAb, mean score 4.1 vs. 3.2 (regression coefficient 0.70; 95% CI 0.1-1.3; P-value 0.02 after adjustment for confounders). The prevalence of a lifetime diagnosis of depression was higher in subjects with positive TPOAb in comparison with participants without TPOAb: 24.2% vs. 16.7% (relative risk 1.4; 95% CI 1.0-2.1; P-value 0.04 after adjustment for confounders). Conclusion: Thyroid peroxidase antibodies are positively associated with trait markers of depression. The presence of TPOAb may be a vulnerability marker for depression.

Traumatic Brain Injury (TBI) is among the most frequent neurological disorders. Of all TBIs 90% are considered mild with an annual incidence of 100–300/100.000. Intracranial complications of Mild Traumatic Brain Injury (MTBI) are infrequent (10%), requiring neurosurgical intervention in a minority of cases (1%), but potentially life-threatening (case fatality rate 0,1%). Hence, a true health management problem exists because of the need to exclude the small chance of a life threatening complication in large numbers of individual patients. The 2002 EFNS guidelines used a best evidence approach based on the literature until 2001 to guide initial management with respect to indications for CT, hospital admission, observation and follow up of MTBI patients. This updated EFNS guideline version for initial management inMTBI proposes a more selectively strategy for CT when major (dangerous mechanism, GCS

Contains fulltext : 109920.pdf (Publisher’s version ) (Closed access) Objective: This study compares inter-rater-reliability, lesion detection and clinical relevance of T2-weighted imaging (T2WI), Fluid Attenuated Inversion Recovery (FLAIR), T2*-gradient recalled echo (T2*-GRE) and Susceptibility Weighted Imaging (SWI) in Traumatic Brain Injury (TBI). Methods: Three raters retrospectively scored 56 TBI patients' MR images (12-76 years old, median TBI-MRI interval 7 weeks) on number, volume, location and intensity. Punctate lesions (diameter /=10 mm). Injury severity was assessed with the Glasgow Coma Scale (GCS), outcome with the Glasgow Outcome Scale-Extended (GOSE). Results: Inter-rater-reliability for lesion volume and punctate lesion count was good (ICC = 0.69-0.94) except for punctate lesion count on T2WI (ICC = 0.19) and FLAIR (ICC = 0.15). SWI showed the highest number of lesions (mean = 30.0), followed by T2*-GRE (mean = 15.4), FLAIR (mean = 3.1) and T2WI (mean = 2.2). Sequences did not differ in detected lesion volume. Punctate lesion count on T2*-GRE (r = -0.53) and SWI (r = -0.49) correlated with the GCS (p < 0.001). Conclusions: T2*-GRE and SWI are more sensitive than T2WI and FLAIR in detecting (haemorrhagic) traumatic punctate lesions. The correlation between number of punctate lesions on T2*-GRE/SWI and the GCS indicates that haemorrhagic lesions are clinically relevant. The considerable inter-rater-disagreement in this study advocates cautiousness in interpretation of punctate lesions using T2WI and FLAIR.

Contains fulltext : 107714.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Prehospital care by physician-based helicopter emergency medical services (P-HEMS) may prolong total prehospital run time. This has raised an issue of debate about the benefits of these services in traumatic brain injury (TBI). We therefore investigated the effects of P-HEMS dispatch on prehospital run time and outcome in severe TBI. METHODS: Prehospital run times of 497 patients with severe TBI who were solely treated by a paramedic EMS (n=125) or an EMS/P-HEMS combination (n=372) were retrospectively analyzed. Other study parameters included the injury severity score (ISS), Glasgow Coma Scale (GCS), prehospital endotracheal intubation and predicted and observed outcome rates. RESULTS: Patients who received P-HEMS care were younger and had higher ISS values than solely EMS-treated patients (10%; P=0.04). The overall prehospital run time was 74+/-54min, with similar out-of-hospital times for EMS and P-HEMS treated patients. Prehospital endotracheal intubation was more frequently performed in the P-HEMS group (88%) than in the EMS group (35%; P

Identifying emotions in people with severe and profound intellectual disabilities is a difficult challenge. Since self-reports are not available, behaviour is the most used source of information. Given the limitations and caveats associated with using behaviour as the sole source of information about their emotions, it is important to supplement behavioural information with informal ion from another source. As it is accepted that emotions consist of language, behaviour and physiology, in this article we investigated if physiology could give information about the emotions of people with severe and profound intellectual disabilities. To this aim we tested hypotheses derived from the motivational model of Bradley, Codispoti, Cuthbert, and Lang (2001) about the relation between heart rate and the valence of emotions and between heart rate, skin conductance and skin temperature and behavioural expressions of emotions of people with severe and profound intellectual disability. We presented 27 participants with 4 staff-selected negative and 4 staff-selected positive stimuli. The situations were videotaped and their heart rate, skin conductance and skin temperature was measured. Each behaviour of the participant was coded using the observational method developed by Petry and Macs (2006). As hypothesized, we found a lower heart rate when participants were presented with negative stimuli than when they were presented with positive stimuli in the first 65 of stimuli presentation. Their skin temperature was higher for the expression of low intensity negative emotions compared to the expression of low intensity positive emotions. The results suggest that, as with people without disability, heart rate and skin temperature can give information about the emotions of persons with severe and profound ID. (C) 2012 Elsevier Ltd. All rights reserved.

Item does not contain fulltext Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP ( approximately 2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 x 10(-8) ) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 x 10(-6) ) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. (c) 2012 Wiley Periodicals, Inc. 01 september 2012

Objective: To determine adherence to Brain Trauma Foundation guidelines for intracranial pressure monitoring after severe traumatic brain injury, to investigate if characteristics of patients treated according to guidelines (ICP+) differ from those who were not (ICP-), and whether guideline compliance is related to 6-month outcome.Design: Observational multicenter study.Patients: Consecutive severe traumatic brain injury patients (>= 16 yrs, n = 265) meeting criteria for intracranial pressure monitoring.Measurements and Main Results: Data on demographics, injury severity, computed tomography findings, and patient management were registered. The Glasgow Outcome Scale Extended was dichotomized into death (Glasgow Outcome Scale Extended = 1) and unfavorable outcome (Glasgow Outcome Scale Extended 1-4). Guideline compliance was 46%. Differences between the monitored and nonmonitored patients included a younger age (median 44 vs. 53 yrs), more abnormal pupillary reactions (52% vs. 32%), and more intracranial pathology (subarachnoid hemorrhage 62% vs. 44%; intraparenchymal lesions 65% vs. 46%) in the ICP+ group. Patients with a total intracranial lesion volume of similar to 150 mL and a midline shift of similar to 12 mm were most likely to receive an intracranial pressure monitor and probabilities decreased with smaller and larger lesions and shifts. Furthermore, compliance was low in patients with no (Traumatic Coma Databank score I -10%) visible intracranial pathology. Differences in case-mix resulted in higher a priori probabilities of dying (median 0.51 vs. 0.35, p Conclusions: Guideline noncompliance was most prominent in patients with minor or very large computed tomography abnormalities. Intracranial pressure monitoring was not associated with 6-month outcome, but multiple baseline differences between monitored and nonmonitored patients underline the complex nature of examining the effect of intracranial pressure monitoring in observational studies. (Crit Care Med 2012; 40:1914-1922)

Item does not contain fulltext Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderate-to-severe TBI patients. Variability in epidemiology and outcome is examined by comparing our cohort with previous multicenter studies. Additionally, the relation between outcome and injury severity classification assessed at different time points is studied. Based on the emergency department Glasgow Coma Scale (GCS), 339 patients were classified as having severe and 129 as having moderate TBI. In 15%, the diagnosis differed when the accident scene GCS was used for classification. In-hospital mortality was higher if severe TBI was diagnosed at both time points (44%) compared to moderate TBI at one or both time points (7-15%, p/=6 h) for impaired consciousness was used as a criterion for severe TBI: In-hospital mortality was

Item does not contain fulltext BACKGROUND: Heterotopic ossification (HO) is a frequent complication after traumatic brain injury (TBI). The current preliminary study is intended to provide additional data on the potential roles that brain injury severity, concomitant orthopaedic trauma, and specific intensive care complicating events may play in the prediction of HO in patients who have sustained severe TBI. METHODS: A prospective cohort study in patients with severe TBI. RESULTS: Ninety-seven of the 176 patients were eligible for follow-up; 13 patients (13%) developed 19 clinically relevant HOs at 1 or more sites. Univariate analysis indicated that patients with HO remained in coma longer (P < .001) and were ventilated during a longer period (P = .002). Autonomic dysregulation (relative risk = 6.11, 95% confidence interval: 2.53-14.76) and surgically treated extremity fractures (relative risk = 5.02, 95% confidence interval: 1.68-15.04) also showed significant associations with the development of HO. CONCLUSION: Prolonged coma duration and mechanical ventilation, coexistent surgically treated bone fractures and clinical signs of autonomic dysregulation should be given further consideration as potential risk factors for developing clinically relevant HO. Larger-scale studies are needed to develop a valid risk profile that takes into account the interrelationships between variables.

Item does not contain fulltext BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of euro386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people. AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country. METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010. RESULTS: The total cost of disorders of the brain was estimated at euro798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between euro285 for headache and euro30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was euro1550 on average but varied by country. The cost (in billion euroPPP 2010) of the disorders of the brain included in this study was as follows: addiction: euro65.7; anxiety disorders: euro74.4; brain tumor: euro5.2; child/adolescent disorders: euro21.3; dementia: euro105.2; eating disorders: euro0.8; epilepsy: euro13.8; headache: euro43.5; mental retardation: euro43.3; mood disorders: euro113.4; multiple sclerosis: euro14.6; neuromuscular disorders: euro7.7; Parkinson's disease: euro13.9; personality disorders: euro27.3; psychotic disorders: euro93.9; sleep disorders: euro35.4; somatoform disorder: euro21.2; stroke: euro64.1; traumatic brain injury: euro33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted euro477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US. DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges. RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives. 01 oktober 2011

Background Because of limited communicative skills, it is not self-evident to measure subjective well-being in people with profound intellectual and multiple disabilities. As a first step towards a non-interprative measure of subjective well-being, we explored how the respiratory, cardiovascular and electro dermal response systems were associated with the valence dimension of emotion. Material and Methods Three participants were presented with staff selected negative and positive stimuli. During the presentation we measured the participants’ respiration, skin conductance, heart rate and respiratory sinus arrhythmia (RSA). We used behavioural codings as an extra measure of emotional valence. Results Participants showed a shallow, fast breathing pattern, used less thoracic breathing, had a higher skin conductance and had less RSA when experiencing positive emotions then when experiencing negative emotions. Conclusion There are physiological differences between positive and negative emotions. The results also indicate that people with PIMD direct their attention away from negative stimuli.

Contains fulltext : 88298.pdf (Publisher’s version ) (Open Access) Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia. 01 september 2010

Contains fulltext : 89903.pdf (Publisher’s version ) (Open Access) Mild traumatic brain injury (mTBI) is a common heterogeneous neurological disorder with a wide range of possible clinical outcomes. Accurate prediction of outcome is desirable for optimal treatment. This study aimed both to identify the demographic, clinical, and computed tomographic (CT) characteristics associated with unfavorable outcome at 6 months after mTBI, and to design a prediction model for application in daily practice. All consecutive mTBI patients (Glasgow Coma Scale [GCS] score: 13-15) admitted to our hospital who were age 16 or older were included during an 8-year period as part of the prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOSE), dichotomized into unfavorable (GOSE score 1-6) and favorable (GOSE score 7-8) outcome groups. The predictive value of several variables was determined using multivariate binary logistic regression analysis. We included 2784 mTBI patients and found CT abnormalities in 20.7% of the 1999 patients that underwent a head CT. Age, extracranial injuries, and day-of-injury alcohol intoxication proved to be the strongest outcome predictors. The presence of facial fractures and the number of hemorrhagic contusions emerged as CT predictors. Furthermore, we showed that the predictive value of a scheme based on a modified Injury Severity Score (ISS), alcohol intoxication, and age equalled the value of one that also included CT characteristics. In fact, it exceeded one that was based on CT characteristics alone. We conclude that, although valuable for the identification of the individual mTBI patient at risk for deterioration and eventual neurosurgical intervention, CT characteristics are imperfect predictors of outcome after mTBI. 01 april 2010

Contains fulltext : 87730.pdf (Publisher’s version ) (Open Access) Computed tomography (CT) of the head has become the diagnostic tool of choice, particularly for moderate and severe traumatic brain injury (TBI). Various CT characteristics are associated with outcome, and may therefore be used as outcome predictors. One of the most prominent predictors appears to be the status of the basal cisterns. This study describes the prognostic value of the appearance of individual cisterns and ventricles in relation to that of the basal cisterns. Further, we determine the interrater and intrarater reliability in the evaluation of the cisterns and ventricles. All consecutive moderate and severe adult TBI patients admitted to our hospital were included in this study as part of the prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOS-E). The predictive value of cisterns and ventricles was determined using multivariate binary logistic regression analysis. We included 126 moderate and 574 severe TBI patients. Absence (complete obliteration), but also compression of the ambient cisterns and/or the fourth ventricle were strongly related to unfavorable outcome and death and emerged as the only significant outcome predictors after multivariate analysis. The assessment of the ambient cisterns and the fourth ventricle had a satisfactory inter- and intrarater reliability (kappa coefficients: 0.80-0.95). We conclude that, because obliteration of the ambient cisterns and the fourth ventricle both are better than the status of the basal cisterns as outcome predictors, they might be used in CT prediction models in cases of moderate and severe TBI. 01 februari 2010

Contains fulltext : 88564.pdf (Publisher’s version ) (Closed access) BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 mug/L for GFAP and 1.13 mug/L for S100B from a previous study. METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS]

Item does not contain fulltext STUDY DESIGN: Literature review. OBJECTIVES: In traumatic spinal cord injury (SCI), much effort has been put into the evaluation of SCI severity and the prediction of recovery potential. An accurate prediction of the initial damage of the spinal cord that differentiates between the severities of SCI however, may help physicians in choosing a particular neuroprotective treatment in the acute phase. Neurochemical biomarkers may possibly fulfil these requirements. The aim of this review was to describe (1) the current status of neurochemical biomarkers in SCI; (2) their potential diagnostic role in SCI. METHODS: MEDLINE was searched from 1966 to 2008 to identify publications concerning biomarkers in traumatic SCI. RESULTS: The biomarkers S-100beta, neuron-specific enolase, neurofilament light chain, and Glial fibrillary acidic protein are significantly increased in cases of (experimental) spinal cord injury. Furthermore, increased serum concentrations of S-100beta have been correlated with an unfavourable functional outcome. Although biomarkers in SCI show promising results, considerations and shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor resuscitation, must be studied in greater detail before biomarkers can be utilised in the clinical care of SCI. CONCLUSIONS: Quantitative standards for determining the extent of SCI during the acute phase must be developed and validated. Even though increased concentrations of neurochemical biomarkers have been identified in patients with SCI, these do not yet provide a sensitive prognostic tool. Considering the limited availability of sensitive prognostic tools, neurochemical biomarkers of SCI should be evaluated and validated in future clinical trials.

Contains fulltext : 71531.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: Functional outcome in patients with minor head injury with neurocranial traumatic findings on CT is largely unknown. We hypothesized that certain CT findings may be predictive of poor functional outcome. Materials and METHODS: All patients from the CT in Head Injury Patients (CHIP) study with neurocranial traumatic CT findings were included. The CHIP study is a prospective, multicenter study of consecutive patients, > or =16 years of age, presenting within 24 hours of blunt head injury, with a Glasgow Coma Scale (GCS) score of 13-14 or a GCS score of 15 and a risk factor. Primary outcome was functional outcome according to the Glasgow Outcome Scale (GOS). Other outcome measures were the modified Rankin Scale (mRS), the Barthel Index (BI), and number and severity of postconcussive symptoms. The association between CT findings and outcome was assessed by using univariable and multivariable regression analysis. RESULTS: GOS was assessed in 237/312 patients (76%) at an average of 15 months after injury. There was full recovery in 150 patients (63%), moderate disability in 70 (30%), severe disability in 7 (3.0%), and death in 10 (4.2%). Outcome according to the mRS and BI was also favorable in most patients, but 82% of patients had postconcussive symptoms. Evidence of parenchymal damage was the only independent predictor of poor functional outcome (odds ratio = 1.89, P = .022). CONCLUSION: Patients with neurocranial complications after minor head injury generally make a good functional recovery, but postconcussive symptoms may persist. Evidence of parenchymal damage on CT was predictive of poor functional outcome.

This study tested whether children's more anxious and avoidant attachment is linked to decreased support-seeking behavior toward their mother during stress in middle childhood, and whether children's decreased support-seeking behavior enhances the impact of experiencing life events on the increase of depressive symptoms 18 months later. Ninety-eight 8- to 12-year-old children filled out questionnaires assessing their level of anxious and avoidant attachment and depressive symptoms. Children's support-seeking behavior was observed through measuring the time children waited before calling for their mother's help while carrying out a stressful task. Results supported the hypothesis that more anxiously or avoidantly attached children waited longer before seeking maternal support. Moreover, waiting longer was related to increased depressive symptoms at follow-up in children who reported more experienced life events. ispartof: Child Development vol:87 issue:1 pages:326-340 ispartof: location:United States status: published

Contains fulltext : 51429.pdf (Publisher’s version ) (Closed access) PURPOSE: To prospectively and externally validate published national and international guidelines for the indications of computed tomography (CT) in patients with a minor head injury. MATERIALS AND METHODS: The study protocol was institutional review board approved. All patients implicitly consented to use of their deidentified data for research purposes. Between February 2002 and August 2004, data were collected in consecutive adult patients with blunt minor head injury (Glasgow Coma Scale score of 13-14 or 15) and a risk factor for neurocranial traumatic complications at presentation at four Dutch university hospitals. Primary outcome was any neurocranial traumatic CT finding. Secondary outcomes were clinically relevant traumatic CT findings and neurosurgical intervention. Sensitivity and specificity of each guideline for all outcomes and the number of patients needed to scan to detect one outcome (ie, the number of patients needed to undergo CT to find one patient with a neurocranial traumatic CT finding, a clinically relevant traumatic CT finding, or a CT finding that required neurosurgical intervention) were estimated. RESULTS: Data were available for 3181 patients. Only the European Federation of Neurological Societies guidelines reached a sensitivity of 100% for all outcomes. Specificity was 0.0%-0.5%. The Dutch guidelines had the lowest sensitivity (76.5%) for neurosurgical interventions. The best specificities for traumatic CT findings and neurosurgical interventions were reached with the criteria proposed by the United Kingdom National Institute for Clinical Excellence (NICE) (46.1% and 43.6%, respectively), albeit at relatively low sensitivities (82.1% and 94.1%, respectively). The number of patients needed to scan ranged from six to 13 for traumatic CT findings and from 79 to 193 for neurosurgical interventions. CONCLUSION: All validated guidelines demonstrated a trade-off between sensitivity and specificity. The lowest number of patients needed to scan for either of the outcomes was reached with the NICE criteria. Supplemental material: radiology.rsnajnls.org/cgi/content/full/2452061509/DC1 (c) RSNA, 2007.

Prostate cancer mortality using current diagnostic tools can be reduced, but at the cost of too many biopsies and overtreatment. Prostate cancer is currently diagnosed using prostate-specic antigen (PSA) testing and systematic ultrasound (sysUS) biopsy. e common PSA test misses 15% of cancers and causes false alarm in 65%–75% of the normal cases, resulting in many unnecessary biopsies. e poor specicity results from elevated PSA levels at benign conditions such as prostatitis or benign prostatic hyperplasia (BPH). Furthermore, sysUS biopsies after PSA testing miss at least 20% of cancers and undergrade the cancers in 50% of the cases. e uncertainty of the tumor aggressiveness leads to overtreatment. Using PSA + sysUS biopsy as screening tool can reduce 25% of prostate cancer mortality (Schroder et al. 2009). However, the amount of unnecessary biopsies and overtreatment is considered too large to justify screening.

Background The underlying mechanism of the juvenile head trauma syndrome (JHTS) is still uncertain, but it has been suggested that there is a role in cortical spreading depression, a phenomenon that is assumed to be a part of the pathophysiology of migraine. Hypothesis We postulate that children affected by the JHTS are more susceptible to cortical spreading depression, caused by a genetic etiology similar to genetic factors in migraine. Methods Children with the JHTS were selected and evaluated retrospectively in an observational case–control study in two Dutch trauma centers in the period between January 2008 and July 2012. Results We included 33 patients with the JHTS, who were accounted for approximately 2.5% of the total number (1,342) of children seen at the emergency department with a mild head trauma. The prevalence of migraine in cases compared with controls did not differ. The proportion of patients with a first-degree relative with migraine was significantly higher in cases compared with controls (odds ratio, 2.69; 95% confidence interval, 1.16–6.22; p = 0.010). Conclusion The JHTS is a relatively rare phenomenon, seen in approximately 2.5% of all children seen at the emergency department with mild brain injury. This study demonstrates a significant relationship between the JHTS and a positive history of migraine in first-degree relatives.