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Contains fulltext : 110491.pdf (Publisher’s version ) (Open Access) ABSTRACT: BACKGROUND: Primary care has an important role in cardiovascular risk management (CVRM) and a minimum size of scale of primary care practices may be needed for efficient delivery of CVRM . We examined CVRM in patients with coronary heart disease (CHD) in primary care and explored the impact of practice size. METHODS: In an observational study in 8 countries we sampled CHD patients in primary care practices and collected data from electronic patient records. Practice samples were stratified according to practice size and urbanisation; patients were selected using coded diagnoses when available. CVRM was measured on the basis of internationally validated quality indicators. In the analyses practice size was defined in terms of number of patients registered of visiting the practice. We performed multilevel regression analyses controlling for patient age and sex. RESULTS: We included 181 practices (63% of the number targeted). Two countries included a convenience sample of practices. Data from 2960 CHD patients were available. Some countries used methods supplemental to coded diagnoses or other inclusion methods introducing potential inclusion bias. We found substantial variation on all CVRM indicators across practices and countries. We computed aggregated practice scores as percentage of patients with a positive outcome. Rates of risk factor recording varied from 55% for physical activity as the mean practice score across all practices (sd 32%) to 94% (sd 10%) for blood pressure. Rates for reaching treatment targets for systolic blood pressure, diastolic blood pressure and LDL cholesterol were 46% (sd 21%), 86% (sd 12%) and 48% (sd 22%) respectively. Rates for providing recommended cholesterol lowering and antiplatelet drugs were around 80%, and 70% received influenza vaccination. Practice size was not associated to indicator scores with one exception: in Slovenia larger practices performed better. Variation was more related to differences between practices than between countries. CONCLUSIONS: CVRM measured by quality indicators showed wide variation within and between countries and possibly leaves room for improvement in all countries involved. Few associations of performance scores with practice size were found.

Contains fulltext : 126635.pdf (Publisher’s version ) (Closed access) Resting-state studies in depressed patients have revealed increased connectivity within the default mode network (DMN) and task-positive network (TPN). This has been associated with heightened rumination, which is the tendency to repetitively think about symptoms of distress. Here, we performed a pharmacological neuroimaging study in healthy volunteers to investigate whether short-term antidepressant administration could reduce DMN connectivity. We recorded resting-state functional magnetic resonance imaging (fMRI) scans in twenty-three healthy volunteers after two week intake of the combined serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine in a double-blind, placebo-controlled, crossover study. Duloxetine improved mood in part as a result of increased resilience to the mood-worsening effects of scanning and reduced DMN and TPN connectivity. Within the DMN, duloxetine reduced connectivity between the medial prefrontal cortex (MPFC) and the lateral parietal cortex (LPC) and uncoupled the MPFC from the dorsolateral prefrontal cortex (DLPFC). Within the TPN, duloxetine uncoupled the intraparietal sulcus (IPS) from the inferior occipital gyrus. These results show that two-week antidepressant administration reduces DMN and TPN connectivity in healthy volunteers, which may contribute to their antidepressant effects in depression.

Contains fulltext : 12563.pdf (Publisher’s version ) (Open Access) BACKGROUND: Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. METHODS: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). RESULTS: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. LIMITATIONS: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. CONCLUSION: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.

Item does not contain fulltext Recent studies show varying results on whether motor imagery capacity is compromised in individuals with cerebral palsy (CP). Motor imagery studies in children predominantly used the implicit hand laterality task. In this task participants judge the laterality of displayed hand stimuli. A more explicit way of studying motor imagery is mental chronometry. This paradigm is based on the comparison between the movement durations of actually performing a task and imagining the same task. The current study explored motor imagery capacity in CP by means of mental chronometry of a whole body task. Movement durations of 20 individuals with CP (mean age = 13 years, SD = 3.6) were recorded in two conditions: actual walking and imagined walking. Six unique trajectories were used that varied in difficulty via manipulation of walking distance and path width. We found no main effect of condition (actual walking versus imagining) on movement durations. Difficulty of the walking trajectory did affect movement durations. In general, this was expressed by an increase in movement durations with increasing difficulty of the task. No interaction between task difficulty and movement condition was found. Our results show that task difficulty has similar effects on movement durations for both actual walking and imagined walking. These results exemplify that the tested individuals were able to use motor imagery in an explicit task involving walking. Previous studies using the implicit hand laterality task showed varying results on motor imagery capacity in CP. We therefore conclude that motor imagery capacity is task dependent and that an explicit paradigm as the one used in this study may reveal the true motor imagery capacity. The implications of these findings for the use of motor imagery training are discussed. 7 p.

Item does not contain fulltext Stress causes the release of many transmitters and hormones, including corticosteroids. These molecules enter the brain and exert their effects through the mineralo- and glucocorticoid receptor. The former receptor plays an important role in neuronal stability. However, it also mediates rapid non-genomic corticosteroid effects that in synergy with other stress mediators activate limbic cells and promote behavioral choices allowing the organism to quickly respond to the imminent danger. Glucocorticoid receptors primarily mediate slow genomic effects, for instance in the hippocampus and prefrontal cortex, which are thought to contribute to contextual and higher cognitive aspects of behavioral performance several hours after stress. Rapid and slow effects interact and collectively contribute to successful behavioral adaptation. Long-term disturbances in the release pattern of corticosteroid hormones and in the responsiveness of their receptors give rise to structural and functional changes in neuronal properties which may contribute to the expression of psychopathology.

Item does not contain fulltext Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity levels of persons with PIMD and to analyze these heart rate patterns according to participant characteristics, observed level of activity, days, and time of day. The heart rate patterns of 24 participants with PIMD were measured continuously using a heart rate monitor for 8 h . d for a period of 6 days. Physical activity levels were measured with questionnaires. Data were analyzed using multilevel analysis. The results indicate that the participants use only 32% of their heart rate reserve over 6 days. The intensity of heart rate reserve ranged from 1 to 62%. On a given day, wide ranges in heart rates between participants and within persons were observed. Between days, only small ranges in the heart rate were found. The participants could be grouped into 4 classes according to their heart rate. In addition, factors such as time of day, physical activity, and age are significantly related to heart rate patterns. In conclusion, this study is an important first step in exploring activity patterns based on heart rate patterns in persons with PIMD. The participants used relatively small fractions of their heart rate reserves. Time of day and age appear to have a considerable influence on heart rate patterns. The observed classes in heart rate patterns suggest that other probably more personal and psychosocial factors have significant influences on heart rate patterns, as well. 01 november 2013

Contains fulltext : 116474.pdf (Publisher’s version ) (Closed access) Objectives: Previous research identified alexithymia as a potential risk factor for substance use disorders (SUD). More insight into the relation between alexithymia and SUD is needed in order to treat SUD effectively. Therefore, we investigated whether a familial vulnerability to alcoholism relates to the presence and severity of alexithymia in SUD patients. Method: Hospitalized, abstinent SUD-patients (n = 187), were assessed with the Toronto Alexithymia Scale (TAS-20) and Addiction Severity Index (EuropASI). A maternal, paternal, and total continuous measure of the Family History of Alcohol (FHA) was developed. Kruskal-Wallis tests and Spearman correlations were used to relate the composite scores of FHA to alexithymia as a categorical and continuous measure. Multivariate regression models were performed to control for the effects of confounders on the relation between FHA and alexithymia. Results: Compared to moderate (33%) and low (17%) alexithymic SUD-patients, high alexithymic (50%) patients were more likely to have fathers with alcohol problems (P = 0.004). Such a difference was not found for mothers with alcohol problems. The composite FHA-score was significantly associated with alexithymia (Rs = .19, P = 0.01). However, only a paternal FHA, independent from disturbed family functioning, related to the degree of alexithymia (beta = .13, P = 0.06), especially to the Difficulty Identifying Feelings as measured by the TAS-20 (beta = .16, P = 0.02). Conclusions: The relation between a paternal FHA and a higher degree of alexithymia in SUD-patients suggests that alexithymia could mediate the familiality of alcoholism or SUD in the paternal line. 7 p.

After hearing a tone, the human auditory system becomes more sensitive to similar tones than to other tones. Current auditory models explain this phenomenon by a simple bandpass attention filter. Here, we demonstrate that auditory attention involves multiple pass-bands around octave-related frequencies above and below the cued tone. Intriguingly, this "octave effect" not only occurs for physically presented tones, but even persists for the missing fundamental in complex tones, and for imagined tones. Our results suggest neural interactions combining octave-related frequencies, likely located in nonprimary cortical regions. We speculate that this connectivity scheme evolved from exposure to natural vibrations containing octave-related spectral peaks, e.g., as produced by vocal cords. ispartof: Proceedings of the National Academy of Sciences of the United States of America vol:110 issue:38 pages:15225-15230 ispartof: location:United States status: published

Although externalizing behavior problems show in general a high stability over time, the course of externalizing behavior problems may vary from individual to individual. Our main goal was to investigate the predictive role of parenting on externalizing behavior problems. In addition, we investigated the potential moderating role of gender and genetic risk (operationalized as familial loading of externalizing behavior problems (FLE), and presence or absence of the dopamine receptor D4 (DRD4) 7-repeat and 4-repeat allele, respectively). Perceived parenting (rejection, emotional warmth, and overprotection) and FLE were assessed in a population-based sample of 1768 10- to 12-year-old adolescents. Externalizing behavior problems were assessed at the same age and 2 1/2 years later by parent report (CBCL) and self-report (YSR). DNA was extracted from blood samples. Parental emotional warmth predicted lower, and parental overprotection and rejection predicted higher levels of externalizing behavior problems. Whereas none of the parenting factors interacted with gender and the DRD4 7-repeat allele, we did find interaction effects with FLE and the DRD4 4-repeat allele. That is, the predictive effect of parental rejection was only observed in adolescents from low FLE families and the predictive effect of parental overprotection was stronger in adolescents not carrying the DRD4 4-repeat allele. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Purpose: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors. Experimental Design: Respiratory chain enzyme assays and 1H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X. Results: In SDHx-related PGLs, a significant decrease in complex II activity (P < 0.0001) and a significant increase in complex I, III, and IV enzyme activities were observed when compared to sporadic, RET, and NF1 tumors. Also, a significant increase in citrate synthase (P < 0.0001) enzyme activity was observed in SDHx-related PGLs when compared to sporadic-, VHL-, RET-, and NF1-related tumors. An increase in succinate accumulation (P < 0.001) and decrease in ATP/ADP/AMP accumulation (P < 0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (P < 0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues. Conclusions: This study for the first time establishes a relationship between determinants of energy metabolism, like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content, and catecholamine content in PGL tumors. Also, this study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with an SDHx mutation. Clin Cancer Res; 19(14); 3787–95. ©2013 AACR.

Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation. One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between cerebrospinal fluid (CSF) and grey matter (Thielscher et al 2011 NeuroImage 54 234-43, Bijsterbosch et al 2012 Med. Biol. Eng. Comput. 50 671-81), or by resizing the whole brain (Wagner et al 2008 Exp. Brain Res. 186 539-50). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images, was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location. © 2013 Institute of Physics and Engineering in Medicine.

Background: The recent introduction of digital hearing aid technology for bone-conduction devices employing percutaneous stimulation may be beneficial for patients with conductive and mixed hearing loss and single sided deafness. Purpose: Performance of a recently released sound processor for bone-anchored implants, the Ponto Pro Power from Oticon Medical (bone-conduction device 2 [BCD2]), was compared with that of the Baha Intenso from Cochlear (bone-conduction device 1 [BCD1]). Research Design: Direct comparison of the subject's own device (BCD1) with the new device (BCD2) was examined in a nonrandomized design. Subjects were initially tested with BCD1. BCD2 was tested after a 4 wk acclimatization period. Study Sample: Eighteen subjects with mixed hearing loss and with at least 4 mo experience with BCD1 completed the study. Mean air-conduction and bone-conduction thresholds averaged across the frequencies of 500, 1000, 2000, and 4000 Hz were 73.9 and 34.2 dB HL, respectively. Data Collection and Analysis: Performance of the two devices was evaluated objectively by measuring aided free-field thresholds, speech perception in quiet, and speech perception in noise. A subjective evaluation was carried out with the Abbreviated Profile of Hearing Aid Benefit (APHAB) (Cox and Alexander, 1995) and the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire (Gatehouse and Noble, 2004). In addition, user experiences, user satisfaction, and device preference were obtained via proprietary questionnaires. Statistical significance was established with analysis-of-variance (ANOVA) and paired t-statistics with Bonferroni correction. Results: Aided free-field thresholds and speech reception thresholds (SRTs) in quiet were not statistically significantly different for either device (p > 0.05). In contrast, SRTs in noise were 2.0 dB lower (p < 0.001) for BCD2 than for BCD1. APHAB questionnaire scores on all subscales provided statistically significantly greater benefit (p < 0.05) for BCD2 than for BCD1. Also, with the SSQ most items in the speech and sound quality domain were significantly more favorable (p < 0.05) for BCD2 than for BCD1. Finally, all subjects preferred BCD2 over BCD1 with 14 subjects reporting a strong preference and four subjects an average preference for the digital signal processing provided by BCD2 over previous technology provided by BCD1.

Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P=0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P=0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P=0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology. (c) 2013 Wiley Periodicals, Inc. Refereed/Peer-reviewed

Item does not contain fulltext BACKGROUND: In 2008 recommendations were launched to prevent medication-related hospital admissions in the Netherlands. Elderly patients using several drugs on a chronic basis were among the target group. Pharmacy-led medication reviews (MRs) were identified as having potential for improving patient safety. OBJECTIVE: This observational study evaluated the implementation success rate of performing all five steps of a complete MR for patients and changes in the presence of nine issues of potentially inappropriate medication (PIM) use. This change was compared between patients with a complete MR (intervention group, IG) and a reference group (RG) who attended the same pharmacy; all patients were eligible for MR, but only selected patients formed the IG. SETTING: Dutch community pharmacy. METHOD: After appropriate training, the rate of IG with complete MRs was measured by pharmacists registering the various MR steps in the MR tool. Patients were eligible for a MR if aged >/= 65 years with >/= 5 drugs being used chronically. MAIN OUTCOME MEASURES: The success rate of implementing MRs with five steps completed; the presence of nine PIMs for both study groups. RESULTS: In pharmacies with specifically trained pharmacists, 63 % of selected patients received a complete MR. This was 12 % higher than in pharmacies without trained pharmacists. PIMs reported at study start declined in the IG and at study end had decreased by an average of 19 % (with a range between 34 and 100 % per PIM); this decrease did not significantly differ from the RG. CONCLUSION: Additional efforts are needed to improve the implementation of pharmacist-led MRs in order to realize its full potential in general practice, and for a substantial decrease of PIMs to occur in susceptible patients. These efforts should focus on training courses and additional support using computerized systems to share information with GPs and to register MR activities, together with sufficient financial reimbursement.

Item does not contain fulltext In modeling the effect of transcranial direct current stimulation, the representation of the skull is an important factor. In a spherical model, we compared a realistic skull modeling approach, in which the skull consisted of three isotropic layers, to anisotropic and isotropic single-layer approximations. We simulated direct current stimulation for a range of conductivity values and investigated differences in the resulting current densities. Our results demonstrate that both approximation methods perform well, provided that the optimal conductivity values are used. We found that for both the anisotropic and the isotropic approximations the optimal conductivity values are largely dictated by the equivalent radial conductivity of the three-layered skull.

Contains fulltext : 128584.pdf (Publisher’s version ) (Closed access) Increased use of stimulant medication, such as methylphenidate, by healthy college students has raised questions about its cognitive-enhancing effects. Methylphenidate acts by increasing extracellular catecholamine levels and is generally accepted to remediate cognitive and reward deficits in patients with attention deficit hyperactivity disorder. However, the cognitive-enhancing effects of such 'smart drugs' in the healthy population are still unclear. Here, we investigated effects of methylphenidate (Ritalin, 20 mg) on reward and punishment learning in healthy students (N=19) in a within-subject, double-blind, placebo-controlled cross-over design. Results revealed that methylphenidate effects varied both as a function of task demands and as a function of baseline working memory capacity. Specifically, methylphenidate improved reward vs punishment learning in high-working memory subjects, whereas it impaired reward vs punishment learning in low-working memory subjects. These results contribute to our understanding of individual differences in the cognitive-enhancing effects of methylphenidate in the healthy population. Moreover, they highlight the importance of taking into account both inter- and intra-individual differences in dopaminergic drug research.

Contains fulltext : 116726.pdf (Publisher’s version ) (Closed access) OBJECTIVE: In a previous article reporting group data, we presented event-related potentials (ERPs), which were evoked by randomly presented target stimuli in a 'learning-oddball' task. These ERPs contained a large N2-P3 complex that decreased and a Contingent Negative Variation (CNV) that increased when the targets were presented in a regular fashion. Using the learning-oddball paradigm, the aim of the present paper was to determine ERP effects of introducing regularity in individual participants. METHODS: The data from the previous study were re-analyzed at the level of the individual participant, extracting individual sigmoid curves by means of wavelet-denoising and focusing on RTs, and CNV, N2, and P3 ERP components. RESULTS: Most participants displayed significant sigmoid curves with respect to the P3 component (22 of the 24 participants - 22/24), the N2 component (20/24), and/or the CNV (19/24) component. In contrast, reaction times (RTs) appeared less sensitive to incidental learning (15/24). Modest correlations were observed between RTs and N2 component amplitudes. CONCLUSIONS: It is possible to extract significant ERP changes to introducing regularity in individual participants. SIGNIFICANCE: Tracking ERP changes within the learning-oddball paradigm might be a useful tool to assess pattern detection capacities in individual patients. 8 p.

In order to investigate the hearing capacities of adult zebrafish (Danio rerio), wild type zebrafish were conditioned to both sound pressure and particle motion in a respondent conditioning paradigm. Sound fields were generated by five underwater loudspeakers in a cylindrical tank, which allows separate control of sound pressure and particle motion. Sound stimuli were soft-switched sound pulses having a strength (RMS) of 0.4 to 5 Pa sound pressure (112 to 134 dB re 1 μPa), 6.7 × 10−7 to 6.7 × 10−6 m/s particle velocity or a combination thereof. Frequencies used were 800 Hz or 250 Hz. During the test a fish was placed in the acoustic centre of the tank, confined in a soft nylon mesh fitted with two silver chloride recording electrodes to measure both changes in position and the ventilatory response. Each sound presentation was followed by a brief mechanical jerk of the fish cage (unconditioned stimulus). The startling response to the unconditioned stimulus was thus coupled to the sound signal (conditioned stimulus). Responses were scored as changes in fish position and/or ventilatory rhythm, occurring during or after the sound pulses, but before the unconditioned stimulus. In this way, we found that wildtype zebrafish respond to artificial sounds having either predominantly sound pressure or particle motion. Discrimination of directionally different sounds could not be established. The method is suited well to probe other auditory capabilities, and to test zebrafish mutants lacking one or more otoliths.

Objectives: Little is known on predictors of hospitalisation in ambulatory patients with chronic heart failure, and known predictors may not apply to Mediterranean countries. Our aim was to document longitudinal trends in hospitalisations and identify patient-related predictors of hospital admission, re-admission and length of stay in the targeted population. Methods: Population-based retrospective cohort study in Catalonia (North-East Spain), including 7196 ambulatory patients (58.6% women; mean age 76 years). Eligible patients were selected from the electronic patient records of primary care practices, and followed for 3 years. Results: At 3 years of follow up overall 645 (9.0%) patients had cardiovascular hospitalisation, 37% were readmitted, and median length of stay was 9 (interquartile range 5-17) days. Chronic kidney disease [odds ratio (OR) = 1.98 (1.62-2.43)], IHD [OR = 1.72 (1.45-2.04)], DM [OR = 1.50 (1.27-1.78)] and chronic obstructive pulmonary disease [OR = 1.43 (1.16-1.77)] increased the risk for hospitalisation. DM [OR = 1.70 (1.22-2.38)], IHD [OR = 1.85 (1.33-2.58)] and HTA [OR = 1.66 (1.11-2.46)] increased the risk for readmissions. Chronic kidney disease [OR of 2.21 (1.70-2.90)], IHD [OR of 2.19 (1.73-2.77)], DM [OR = 1.70 (1.34-2.15)], HTA [OR = 1.51 (1.13-2.01)], chronic obstructive pulmonary disease [OR = 1.37 (1.02-1.83)] increased the risk for long length of stay in hospital. Conclusions: Our study identified predictors of hospitalisation, readmissions and long length of stay which can help clinicians and managers to identify high risk patients which should be targeted on service planning and when designing preventive actions. © 2012 Elsevier España, S.L.

Item does not contain fulltext Rationale, aims and objectives In most countries, different health care providers are involved in emergency care. In the Netherlands, out-of-hours care is provided by general practitioner cooperatives (GPCs) and emergency departments (EDs). Our aim was to describe the flow of patients attending emergency care in these settings. Method A retrospective record review was performed, concerning patients who had visited a GPC or ED. Recorded information included urgency, diagnostic tests, and follow-up contacts. Descriptive figures were determined for patient flows in GPC and ED for urgent contacts and non-urgent contacts. Results We included 319 GPC contacts and 356 ED contacts, of which 78% were non-urgent. The majority of GPC contacts were completed at the GPC without follow-up; 37% of non-urgent patients had a follow-up contact, usually with primary care. Only 5% of non-urgent GPC patients received diagnostic tests compared to 63% of non-urgent ED patients (mostly X-rays). The majority of non-urgent ED patients (88%) had a follow-up contact, usually at an outpatient clinic (67%). Most non-urgent ED patients (83%) who received a diagnostic test also had an outpatient clinic follow-up contact. Of urgent ED patients, the majority had a follow-up contact (85%), mostly with an outpatient clinic (74%). Conclusion Although most out-of-hours care patients present non-urgent health problems, at the ED they are more likely to receive diagnostic tests and follow-up contacts. This may reflect differences in patient populations between the ED and GPC or suggest opportunities for improving efficiency of planning follow-up contacts.

Contains fulltext : 188545.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext This contribution discusses the feasibility of extracting the major features of repolarization: its spatio-temporal behaviour, and how much of its global or local behaviour might be deduced from signals that can be observed experimentally. The analysis presented is based on source-volume-conductor configurations ranging from the classic cable theory, with sources derived from reaction diffusion computations, to a realistic thorax model comprising a whole heart model with electric sources represented by the equivalent electric double layer. The analysis focuses on the fact that the local activation recovery interval (ARI) at regions activated by expanding wave fronts is significantly longer than those activated by contracting ones. The consequences of this effect on observed magnitude and wave form of recorded signals are illustrated.

Contains fulltext : 117242.pdf (Publisher’s version ) (Closed access) It is unclear whether top-down processing in the auditory cortex (AC) interferes with its bottom-up analysis of sound. Recent studies indicated non-acoustic modulations of AC responses, and that attention changes a neuron's spectrotemporal tuning. As a result, the AC would seem ill-suited to represent a stable acoustic environment, which is deemed crucial for auditory perception. To assess whether top-down signals influence acoustic tuning in tasks without directed attention, we compared monkey single-unit AC responses to dynamic spectrotemporal sounds under different behavioral conditions. Recordings were mostly made from neurons located in primary fields (primary AC and area R of the AC) that were well tuned to pure tones, with short onset latencies. We demonstrated that responses in the AC were substantially modulated during an auditory detection task and that these modulations were systematically related to top-down processes. Importantly, despite these significant modulations, the spectrotemporal receptive fields of all neurons remained remarkably stable. Our results suggest multiplexed encoding of bottom-up acoustic and top-down task-related signals at single AC neurons. This mechanism preserves a stable representation of the acoustic environment despite strong non-acoustic modulations. 13 p.

Contains fulltext : 119214.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext AIM: The purpose of this study was to assess the relation of perinatal risk factors with later development of specific language impairment (SLI). METHOD: In a case-control study, 179 children attending special needs schools for SLI were matched with non-affected children attending mainstream schools. Both groups consisted of 134 males and 45 females (age range 4-13y; mean age 9y, SD 2y 4mo). Data on duration of pregnancy, birthweight, delivery complications, birth characteristics, and Apgar scores were collected from the Preventive Child Health Care files of the Municipal Health Service. RESULTS: The gestational age of the children with SLI (mean 39.6wks, SD 0.1wk) and for the comparison group (mean 39.4wks, SD 0.1wk) and the birthweight of children with SLI (mean 3330.4g; SD 41.4g) and for the comparison group (mean 3388.1g; SD 39.8g) were not statistically different; neither were other pregnancy and birth characteristics, with the exception of the Apgar scores (effect of group for Apgar score after 1min p=0.045; after 5min p=0.001). The difference in Apgar scores was larger for females than for males (effect of group x sex for Apgar score after 1min p=0.049; after 5min p=0.043). INTERPRETATION: The relation between Apgar scores and SLI together with the influence of sex may be meaningful for predicting modelling and for understanding the causal pathway for SLI.

Item does not contain fulltext OBJECTIVE: Little is known about patient safety in primary oral healthcare. The aim of this study was to describe and analyze patient safety incidents in primary oral health care. MATERIALS AND METHODS: A random sample of 1000 patient records from 20 dental practices was reviewed retrospectively over 60 months. All adverse events (AEs) were noted: unintended events happening during treatment that resulted or could have resulted in harm to the patient. RESULTS: A total of 46 (95% CI = 33-59) AEs was identified, of which 18 (95% CI = 10-26) were considered preventable. From these, 15 related to treatment, 10 to diagnostics and one to communication. CONCLUSIONS: The low incidence of AEs and absence of major harm to patients suggests that primary oral care is safe for patients. However, the low quality of record keeping may imply underestimation.

Contains fulltext : 117935.pdf (Publisher’s version ) (Closed access) OBJECTIVE: : To estimate whether a strategy of immediate surgery was noninferior to a strategy based on discordant urodynamic findings followed by individually tailored therapy in women with stress urinary incontinence (SUI). METHODS: : A multicenter diagnostic cohort study with an embedded noninferiority randomized controlled trial was conducted in six academic and 24 nonacademic Dutch hospitals. Women with predominant SUI eligible for surgical treatment based on clinical assessment were included between January 2009 and November 2010. All patients underwent urodynamics. In patients in whom urodynamics were discordant with clinical assessment, participants were randomly allocated to receive either immediate surgery or individually tailored therapy based on urodynamics. The primary outcome was clinical improvement assessed by the Urogenital Distress Inventory 12 months after baseline. Analysis was by intention to treat; a difference in mean improvement of 5 points or less was considered noninferior. RESULTS: : Five hundred seventy-eight women with SUI were studied, of whom 268 (46%) had discordant findings. One hundred twenty-six patients gave informed consent for randomization and were allocated to receive immediate surgery (n=64) or individually tailored therapy (n=62). The mean improvement measured with the Urogenital Distress Inventory after 1 year was 44 points (+/-24) in the group receiving immediate surgery and 39 (+/-25) points in the group receiving individually tailored treatment. The difference in mean improvement was 5 points in favor of the group receiving immediate surgery (95% confidence interval -infinity to 5). There were no differences with respect to cure or complication rate. CONCLUSION: : In women with uncomplicated SUI, an immediate midurethral sling operation is not inferior to individually tailored treatment based on urodynamic findings. CLINICAL TRIAL REGISTRATION: : ClinicalTrials.gov, www.clinicaltrials.gov, NCT00814749. LEVEL OF EVIDENCE: : I.

Contains fulltext : 115407.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with major depressive disorder (MDD) display impairments in recollection, which have been explained by both hippocampal and prefrontal dysfunction. Here, we used an event-related fMRI design, to dissociate hippocampal and prefrontal contributions to the neural processes involved in recollection success and recollection attempt early in the course of MDD. METHODS: To disentangle state- and trait-effects of depression, we included 20 medication-naive patients with a first depressive episode, 20 medication-free patients recovered from a first episode, and 20 matched, healthy controls in an event-related fMRI study using a source recollection paradigm. RESULTS: Group comparisons revealed that during the acute state of depression there is an increase in left prefrontal activity related to recollection attempt, while there were no differences in neural correlates of successful recollection. CONCLUSIONS: Our results indicate that in the early course of depression, depressive state is associated with increased left prefrontal activation during the attempt to recollect source information suggesting an increased need for executive control during recollection in MDD. In this sample of first-episode MDD patients we found no evidence for hippocampal dysfunction.

Item does not contain fulltext OBJECTIVE: To investigate the quality of life of people with an auricular prosthesis. METHODS: A retrospective case series study was conducted. Quality of life was evaluated by an open-ended question form and 3 questionnaires: the Glasgow Benefit Inventory, the Rosenberg Self-Esteem scale, and the standard Medical Outcome Study Short-Form 12. The occurrence of peri-implant skin reactions (defined by Holgers), along with fixture stability and prosthesis data, were evaluated in 29 implants from 10 patients. The follow-up period varied between several months and more than 17 years. RESULTS: The 3 questionnaires showed an improvement in quality of life scores for all patients, and all patients would recommend the prosthesis. Skin reactions that needed treatment (ie, Holgers grades 2-4) were seen in 6.2% of all observations; 44.8% of the implants demonstrated either no reaction at all or redness only around the implant. A significant correlation was found between the Rosenberg Self-Esteem score and the number of prosthesis replacements. CONCLUSION: In general, patients seemed to be satisfied with the auricular prostheses, which did improve their quality of life. Furthermore, the quality of life was enhanced with higher quality prostheses and with proper hygiene to prevent skin reactions.

Contains fulltext : 116831.pdf (Publisher’s version ) (Open Access) Aim To investigate the validity and reliability of the revised Video-Observation Aarts and Aarts module: Determine Developmental Disregard (VOAA-DDD-R). Method Upper-limb capacity and performance were assessed in children with unilateral spastic cerebral palsy (CP) by measuring overall duration of affected upper-limb use and the frequency of specific behaviours during a task in which bimanual activity was demanded (stringing beads) and stimulated (decorating a muffin). Developmental disregard was defined as the difference in duration of affected upper-limb use between both tasks. Raters were two occupational and one physical therapist who received 3 hours of training. Construct validity was determined by comparing children with CP with typically developing children. Intrarater, interrater, and testretest reliability were determined using the intraclass correlation coefficient. Standard errors of measurement and smallest detectable differences were also calculated. Results Twenty-five children with CP (15 females, 10 males; mean age 4y 9mo [SD 1y 7mo], range 2y 9mo8y; Manual Ability Classification System levels IIII) scored lower on capacity (p=0.052) and performance (p

Item does not contain fulltext BACKGROUND: Job satisfaction of practice staff is important for optimal health care delivery and for minimizing the turnover of non-medical professions. OBJECTIVE: To document the job satisfaction of practice assistants in German general practice and to explore associations between job satisfaction, staff characteristics and culture in general practice organizations. METHODS: The study was based on data from the European Practice Assessment accreditation scheme for general practices and used an observational design. The study population consisted of 1158 practice assistants from 345 general practices across Germany. Job satisfaction was measured with the 10-item Warr-Cook-Wall questionnaire. Organizational culture was evaluated with four items. A linear regression analysis was performed in which each of the job satisfaction items was handled as dependent variable. RESULTS: Out of 1716 staff member questionnaires handed out to practice assistants, 1158 questionnaires were completed (response rate: 67.5%). Practice assistants were most satisfied with their colleagues and least satisfied with their income. Higher job satisfaction was associated with issues of organizational culture, particularly a good working atmosphere, opportunities to suggest and influence areas for improvement and clear responsibilities within the practice team. CONCLUSIONS: Prioritizing initiatives to maintain high levels of, or to improve the job satisfaction of practice assistants, is important for recruitment and retention. It will also help to improve working conditions for both practice assistants and GPs and create an environment to provide better quality care.

OBJECTIVE: To assess the clinical effectiveness of bilateral cochlear implantation compared with unilateral cochlear implantation alone or with a contralateral hearing aid (bimodal stimulation), in children with severe-to-profound hearing loss. Recently, the National Institute for Health and Clinical Excellence (NICE) in the U.K. has conducted a systematic review on cochlear implantation. We decided to update the pediatric part of the NICE review. DATA SOURCES: The electronic databases MEDLINE and Embase were searched for European, North American, and Australasian studies published between October 2006 and June 2009. Reference lists of the included articles were also searched for relevant articles. STUDY SELECTION: Studies were included if they comprised data on comparisons between bilateral cochlear implantation and unilateral cochlear implantation and/or bilateral cochlear implantation and bimodal stimulation, in children with severe-to-profound sensorineural hearing loss. The following outcome measures were analyzed: audiological, speech perception, speech production, functional capacities, health-related quality of life, and/or educational outcomes. DATA EXTRACTION: Characteristics of the participants, interventions, outcomes, and methodological comments were entered into data extraction forms and the level of evidence was assessed. DATA SYNTHESIS: Results were standardized for each outcome measure by calculating a standardized mean difference (effect size). CONCLUSION: Effect sizes could not be pooled because of the heterogeneity of the studies. Therefore, we presented the results qualitatively. Although the level of evidence was low, the advantages of bilateral cochlear implants corresponded with the primary benefits of bilateral hearing, that is, improved speech perception in quiet and noise. Localization results were less consistent. No data on audiologic, speech production, or educational outcomes were available.

Item does not contain fulltext Since deafness is the most common sensorineural disorder in humans, better understanding of the underlying causes is necessary to improve counseling and rehabilitation. A Dutch family with autosomal dominantly inherited sensorineural hearing loss was clinically and genetically assessed. The MYO6 gene was selected to be sequenced because of similarities with other, previously described DFNA22 phenotypes and a pathogenic c.3610C > T (p.R1204W) mutation was found to co-segregate with the disease. This missense mutation results in a flat configured audiogram with a mild hearing loss, which becomes severe to profound and gently to steeply downsloping later in life. The age-related typical audiograms (ARTA) constructed for this family resemble presbyacusis. Speech audiometry and results of loudness scaling support the hypothesis that the phenotype of this specific MYO6 mutation mimics presbyacusis.

BackgroundPathological gambling (PG) is an impulse control disorder characterized by excessive monetary risk seeking in the face of negative consequences. We used tools from the field of behavioral economics to refine our description of risk-taking behavior in pathological gamblers. This theoretical framework allowed us to confront two hypotheses: (1) pathological gamblers distort winning probabilities more than controls; and (2) pathological gamblers merely overweight the whole probability range.MethodEighteen pathological gamblers and 20 matched healthy participants performed a decision-making task involving choices between safe amounts of money and risky gambles. The online adjustment of safe amounts, depending on participants' decisions, allowed us to compute ‘certainty equivalents’ reflecting the subjective probability weight associated with each gamble. The behavioral data were then fitted with a mathematical function known as the ‘probability weighting function’, allowing us to disentangle our two hypotheses.ResultsThe results favored the second hypothesis, suggesting that pathological gamblers' behavior reflects economic preferences globally shifted towards risk, rather than excessively distorted probability weighting. A mathematical parameter (elevation parameter) estimated by our fitting procedure was found to correlate with gambling severity among pathological gamblers, and with gambling affinity among controls.ConclusionsPG is associated with a specific pattern of economic preferences, characterized by a global (i.e. probability independent) shift towards risky options. The observed correlation with gambling severity suggests that the present ‘certainty equivalent’ task may be relevant for clinical use.

Contains fulltext : 125471.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 444285.pdf (Publisher’s version ) (Open Access) Compromised action performance is one of the most characteristic features of children with unilateral spastic cerebral palsy (USCP). Current rehabilitation efforts predominantly aim to improve the capacity and performance of the affected arm. Recent evidence, however, suggests that compromised motor planning may also negatively affect performance of activities of daily living. In this paper we will first discuss the recent evidence for this motor planning deficit, followed by studies on motor imagery in this population. Motor imagery is an experimental approach in which the contents of the motor plan become overt. Converging evidence indicates a compromised motor imagery ability in USCP. As the neural structures of both motor planning and motor imagery overlap, rehabilitation by motor imagery training may alleviate motor problems in USCP. Increasing evidence for this approach exists in older adults with stroke. We conclude this review with recommendations on such a training approach for children with USCP. 01 november 2013 4 p.

Item does not contain fulltext OBJECTIVE: Our aim was to assess cost-effectiveness of mindfulness-based cognitive therapy (MBCT) compared with enhanced usual care (EUC) in treating patients with persistent medically unexplained symptoms(MUS). METHODS: A full economic evaluation with a one year time horizon was performed from a societal perspective. Costs were assessed by prospective cost diaries. Health-related Quality of Life was measured using SF-6D. Outcomes were costs per Quality-Adjusted Life Year (QALY). Bootstrap simulations were performed to obtain mean costs, QALY scores and incremental cost-effectiveness ratios (ICERs). RESULTS: MBCT participants (n=55) had lower hospital costs and higher mental health care costs than patients who received EUC (n=41). Mean bootstrapped costs for MBCT were euro6269, and euro5617 for EUC (95% uncertainty interval for difference: -euro1576; euro2955). QALYs were 0.674 for MBCT and 0.663 for EUC. MBCT was on average more effective and more costly than EUC, resulting in an ICER of euro56,637 per QALY gained. At a willingness to pay of euro80,000 per QALY, the probability that MBCT is cost-effective is 57%. CONCLUSION: Total costs were not statistically significantly different between MBCT and EUC. However, MBCT seemed to cause a shift in the use of health care resources as mental health care costs were higher and hospital care costs lower in the MBCT condition. Due to the higher drop-out in the EUC condition the cost-effectiveness of MBCT might have been underestimated. The shift in health care use might lead to more effective care for patients with persistent MUS. The longer-term impact of MBCT for patients with persistent MUS needs to be further studied.

Item does not contain fulltext OBJECTIVES: Despite good results on osseointegration and limited skin reactions with percutaneous bone conductors, there remains room for improvement. Especially in children, adverse events with percutaneous bone conductors might occur more frequently. Transcutaneous bone conductors, if powerful enough, can provide a solution that minimizes adverse events and implant loss. This study compares a new transcutaneous bone conduction hearing aid, the Sophono Alpha 1 (Sophono), with the percutaneous BAHA system (BAHA). METHODS: In our tertiary referral center, 12 patients (age 5-12 yr) with congenital unilateral conductive hearing loss were enrolled in the study as follows: 6 patients with the Sophono and 6 with the BAHA. Both clinical results and audiologic data were gathered. For an objective audiologic comparison between both systems, we used a skull simulator. RESULTS: The skin reactions were comparable between both groups, in 1 implant was lost 1 month after second phase surgery (BAHA). The users received audiologic benefits from both systems. The BAHA-based outcome was slightly better compared with Sophono-based results in sound field thresholds, speech recognition threshold, and speech comprehension at 65 dB. The skull simulator demonstrated that the BAHA device has an output that is 10 to 15 dB higher compared with the Sophono device. CONCLUSION: The Sophono offers appealing clinical benefits of transcutaneous bone conduction hearing; however, the audiologic challenges of transcutaneous application remain, as the Sophono does not exceed percutaneous application regarding audiologic output.

Item does not contain fulltext Concurring with the shift from linking functions to specific brain areas towards studying network integration, resting state FMRI (R-FMRI) has become an important tool for delineating the functional network architecture of the brain. Fueled by straightforward data collection, R-FMRI analysis methods as well as studies reporting on R-FMRI have flourished, and already impact research on child- and adolescent psychiatric disorders. Here, we review R-FMRI analysis techniques and outline current methodological debates. Furthermore, we provide an overview of the main R-FMRI findings related to child- and adolescent psychiatric disorders. R-FMRI research has contributed significantly to our understanding of brain function in child and adolescent psychiatry: existing hypotheses based on task-based FMRI were confirmed and new insights into the brain's functional architecture of disorders were established. However, results were not always consistent. While resting state networks are robust and reproducible, neuroimaging research in psychiatric disorders is especially complicated by tremendous phenotypic heterogeneity. It is imperative that we overcome this heterogeneity when integrating neuroimaging into the diagnostic and treatment process. As R-FMRI allows investigating the richness of the human functional connectome and can be easily collected and aggregated into large-scale datasets, it is clear that R-FMRI can be a powerful tool in our quest to understand psychiatric pathology.

Current theories propose that coherence of oscillatory brain activity in the gamma band (30-80 Hz) constitutes an avenue for communication among remote neural populations. However, reports documenting stimulus dependency and time variability of gamma frequency suggest that distant neuronal populations may, at any one time, operate at different frequencies precluding synchronization. To test this idea, we recorded from macaque V1 and V2 simultaneously while presenting gratings of varying contrast. Although gamma frequency increased with stimulus contrast in V1 and V2 (by approximately 25 Hz), V1-V2 gamma coherence was maintained for all contrasts. Moreover, while gamma frequency fluctuated by approximately 15 Hz during constant contrast stimulation, this fluctuation was highly correlated between V1 and V2. The strongest coherence connections showed a layer-specific pattern, matching feedforward anatomical connectivity. Hence, gamma coherence among remote populations can occur despite large stimulus-induced and time-dependent changes in gamma frequency, allowing communication through coherence to operate without a stimulus independent, fixed-frequency gamma channel.

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Item does not contain fulltext Spinocerebellar ataxias are phenotypically, neuropathologically, and genetically heterogeneous. The locus of autosomal recessive spinocerebellar ataxia type 7 (SCAR7) was previously linked to chromosome band 11p15. We have identified TPP1 as the causative gene for SCAR7 by exome sequencing. A missense and a splice site variant in TPP1, cosegregating with the disease, were found in a previously described SCAR7 family and also in another patient with a SCAR7 phenotype. TPP1, encoding the tripeptidyl-peptidase 1 enzyme, is known as the causative gene for late infantile neuronal ceroid lipofuscinosis disease 2 (CLN2 disease). CLN2 disease is characterized by epilepsy, loss of vision, ataxia, and a rapidly progressive course, leading to early death. SCAR7 patients showed ataxia and low activity of tripeptidyl-peptidase 1, but no ophthalmologic abnormalities or epilepsy. Also, the slowly progressive evolution of the disease until old age and absence of ultra structural curvilinear profiles is different from the known CLN2 phenotypes. Our findings now expand the phenotypes related to TPP1-variants to SCAR7. In spite of the limited sample size and measurements, a putative genotype-phenotype correlation may be drawn: we hypothesize that loss of function variants abolishing TPP1 enzyme activity lead to CLN2 disease, whereas variants that diminish TPP1 enzyme activity lead to SCAR7.

Contains fulltext : 118055.pdf (Publisher’s version ) (Closed access) The objective of this study is to determine the benefits of bone-anchored hearing aid (Baha) contralateral routing of signal (CROS) in the older adult population with single-sided deafness. Five questionnaires [general usage questionnaire, Glasgow benefit inventory (GBI), Abbreviated profile of hearing aid benefit (APHAB), Nijmegen cochlear implant questionnaire and the hearing handicap inventory for the elderly-screening version (HHIE-S)] were used to evaluate Baha use. Consecutive patients over 60 years of age with SSD fitted with a Baha CROS between April 1990 and April 2007 not using a conventional hearing aid in the better-hearing ear were identified. Nine out of 11 patients (82 %) were still using their Baha CROS, and 7 of the 11 patients (64 %) were still satisfied. The patients experienced no to little problems with handling and cleaning of the device. The GBI scores show good benefit in domains total (14 +/- 11) and general (19 +/- 17). The APHAB shows that, overall, 3 out of the 11 patients (27 %) experienced significant benefit, while all others experienced no significant benefit and no drawbacks. The HHIE-S shows that the patients experienced severe (18 %), mild to moderate (46 %) or no handicap (36 %) when using the Baha CROS. In conclusion, the benefit of a Baha CROS for elderly patients with SSD is evident in the majority of patients.

Schizophrenia research has identified deficits in neurocognition, social cognition, and sensory processing. Because a cohesive model of “disturbed cognitive machinery” is currently lacking, we built a conceptual model to integrate neurocognition, social cognition, and sensory processing.In a cross-sectional study, the cognitive performance of participants was measured. In accordance with the Schedules for Clinical Assessment in Neuropsychiatry, the participants were assigned to either the schizophrenia group or the non-schizophrenic psychosis group. Exclusion criteria included substance abuse, serious somatic/neurological illness, and perceptual handicap. The male/female ratio, educational level, and handedness did not differ significantly between the groups.The data were analyzed using structural equation modeling. Based upon the results of all possible pairwise models correlating neurocognition, social cognition, and sensory processing, three omnibus models were analyzed. A statistical analysis of a pairwise model-fit (χ2, CFI, and RMSEA statistics) revealed poor interrelatedness between sensory processing and neurocognition in schizophrenia patients compared with healthy control participants. The omnibus model that predicted disintegration between sensory processing and neurocognition was statistically confirmed as superior for the schizophrenia group (χ2(53) of 56.62, p = 0.341, RMSEA = 0.04, CFI = 0.95). In healthy participants, the model predicting maximal interrelatedness between sensory processing/neurocognition and neurocognition/social cognition gave the best fit (χ2(52) of 53.74, p = 0.408, RMSEA = 0.03, CFI = 0.97). The performance of the patients with non-schizophrenic psychosis fell between the schizophrenia patients and control participants.These findings suggest increasing separation between sensory processing and neurocognition along the continuum from mental health to schizophrenia. Our results support a conceptual model that posits disintegration between sensory processing of social stimuli and neurocognitive processing.Keywords: Schizophreni, Psychosis, Cognition, Sensory processing, Disintegration, Structural equation modeling

Item does not contain fulltext OBJECTIVE: A double-blind, randomized, placebo-controlled study was designed to assess the efficacy and safety of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD). The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen, The Netherlands. METHOD: Forty-one children (aged 8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly assigned to treatment with either EEG neurofeedback (n = 22) or placebo neurofeedback (n = 19) for 30 sessions, given as 2 sessions per week. The children were stratified by age, electrophysiologic state of arousal, and medication use. Everyone involved in the study, except the neurofeedback therapist and the principal investigator, was blinded to treatment assignment. The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV, scored at baseline, during treatment, and at study end. Clinical improvement as measured by the Clinical Global Impressions-Improvement scale (CGI-I) was a secondary outcome. RESULTS: While total ADHD symptoms improved over time in both groups (F1,39 = 26.56, P < .001), there was no significant treatment effect, ie, group x time interaction (F1,39 = 0.36, P = .554); the same was true for clinical improvement as measured by the CGI-I (P = .092). No clinically relevant side effects were observed. Among the children and their parents, guessing treatment assignment was not better than chance level (P = .224 for children, P = .643 for parents). CONCLUSION: EEG neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00723684.

Contains fulltext : 125880.pdf (Publisher’s version ) (Open Access) It is often assumed that decision making involves neural competition, accumulation of evidence "scores" over time, and commitment to a particular alternative once its scores reach a critical decision threshold first. So far, however, neither the first-to-threshold rule nor the nature of competition (feedforward or feedback inhibition) has been revealed by experiments. Here, we presented two simultaneously flashed targets that reversed their intensity difference during each presentation and instructed human subjects to make a saccade toward the brightest target. All subjects preferentially chose the target that was brightest during the first stimulus phase. Unless this first phase lasted only 40 ms, this primacy effect persisted even if the second, reversed-intensity phase lasted longer. This effect did not result from premature commitment to the initially dominant target, because a strong target imbalance in the opposite direction later drove nearly all responses toward that location. Moreover, there was a nonmonotonic relation between target imbalance and primacy: increasing the target imbalance beyond 40 cd/m(2) caused an attenuation of primacy. These are the hallmarks of hysteresis, predicted by models in which target representations compete through strong feedback. Reaction times were independent of the choice probability. This dissociation suggests that target selection and movement initiation are distinct phenomena.

Item does not contain fulltext Orienting responses to audiovisual events have shorter reaction times and better accuracy and precision when images and sounds in the environment are aligned in space and time. How the brain constructs an integrated audiovisual percept is a computational puzzle because the auditory and visual senses are represented in different reference frames: the retina encodes visual locations with respect to the eyes; whereas the sound localisation cues are referenced to the head. In the well-known ventriloquist effect, the auditory spatial percept of the ventriloquist's voice is attracted toward the synchronous visual image of the dummy, but does this visual bias on sound localisation operate in a common reference frame by correctly taking into account eye and head position? Here we studied this question by independently varying initial eye and head orientations, and the amount of audiovisual spatial mismatch. Human subjects pointed head and/or gaze to auditory targets in elevation, and were instructed to ignore co-occurring visual distracters. Results demonstrate that different initial head and eye orientations are accurately and appropriately incorporated into an audiovisual response. Effectively, sounds and images are perceptually fused according to their physical locations in space independent of an observer's point of view. Implications for neurophysiological findings and modelling efforts that aim to reconcile sensory and motor signals for goal-directed behaviour are discussed.

OBJECTIVE To confirm the clinical efficacy and safety of a direct acoustic cochlear implant. STUDY DESIGN Prospective multicenter study. SETTING The study was performed at 3 university hospitals in Europe (Germany, The Netherlands, and Switzerland). PATIENTS Fifteen patients with severe-to-profound mixed hearing loss because of otosclerosis or previous failed stapes surgery. INTERVENTION Implantation with a Codacs direct acoustic cochlear implant investigational device (ID) combined with a stapedotomy with a conventional stapes prosthesis MAIN OUTCOME MEASURES Preoperative and postoperative (3 months after activation of the investigational direct acoustic cochlear implant) audiometric evaluation measuring conventional pure tone and speech audiometry, tympanometry, aided thresholds in sound field and hearing difficulty by the Abbreviated Profile of Hearing Aid Benefit questionnaire. RESULTS The preoperative and postoperative air and bone conduction thresholds did not change significantly by the implantation with the investigational Direct Acoustic Cochlear Implant. The mean sound field thresholds (0.25-8 kHz) improved significantly by 48 dB. The word recognition scores (WRS) at 50, 65, and 80 dB SPL improved significantly by 30.4%, 75%, and 78.2%, respectively, after implantation with the investigational direct acoustic cochlear implant compared with the preoperative unaided condition. The difficulty in hearing, measured by the Abbreviated Profile of Hearing Aid Benefit, decreased by 27% after implantation with the investigational direct acoustic cochlear implant. CONCLUSION Patients with moderate-to-severe mixed hearing loss because of otosclerosis can benefit substantially using the Codacs investigational device.

Objective. Many patients with schizophrenia are not treated in line with evidence-based guidelines. This study examines the large-scale implementation of the National Multidisciplinary Guideline for schizophrenia in the Netherlands. Design. Observational, prospective study, with repeated measurement. Setting. Thirty mental healthcare teams in different regions of the Netherlands. Participants. Three hundred and fifty-nine clinicians with different professional backgrounds and 1489 patients suffering from schizophrenia. Intervention(s). Six evidence-based interventions for schizophrenia were implemented, in the context of a quality improvement collaborative: assertive community treatment (ACT) or its adapted version functional assertive community treatment (FACT), cognitive behavioural therapy, psycho-education, family interventions, individual placement support and pharmacotherapy. Main Outcome Measure(s). Professional performance, social functioning and relapse rates. Results. Improved professional performance, in line with guidelines. Availability of (F)ACT improved from 23 to 60%. Individual Placement Support improved from 20 to 53%. Complete care plans were composed for 38% of the patients and routine outcome monitoring was introduced in most teams. Social functioning improved slightly (HoNOS mean: from 6.2 to 5.6). Relapse rates did not improve during the course of the study. Conclusions. An intensive implementation programme can result in an improved delivery of evidence-based care, increased continuity of care and slightly improved outcomes for individuals with schizophrenia. More rigorous research designs have to confirm these findings. © The Author 2013. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Contains fulltext : 118482.pdf (Publisher’s version ) (Open Access) BACKGROUND: Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach. METHODS: We conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p