The Association Between Stuttering Burden and Psychosocial Aspects of Life in Adults.

PURPOSE: Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life. METHOD: The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden. RESULTS: We identified a high- (n = 230) and a low-burden subgroup (n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden. CONCLUSIONS: Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25582980.

Comparison of stochastic and deterministic models for gambiense sleeping sickness at different spatial scales: A health area analysis in the DRC.

The intensification of intervention activities against the fatal vector-borne disease gambiense human African trypanosomiasis (gHAT, sleeping sickness) in the last two decades has led to a large decline in the number of annually reported cases. However, while we move closer to achieving the ambitious target of elimination of transmission (EoT) to humans, pockets of infection remain, and it becomes increasingly important to quantitatively assess if different regions are on track for elimination, and where intervention efforts should be focused. We present a previously developed stochastic mathematical model for gHAT in the Democratic Republic of Congo (DRC) and show that this same formulation is able to capture the dynamics of gHAT observed at the health area level (approximately 10,000 people). This analysis was the first time any stochastic gHAT model has been fitted directly to case data and allows us to better quantify the uncertainty in our results. The analysis focuses on utilising a particle filter Markov chain Monte Carlo (MCMC) methodology to fit the model to the data from 16 health areas of Mosango health zone in Kwilu province as a case study. The spatial heterogeneity in cases is reflected in modelling results, where we predict that under the current intervention strategies, the health area of Kinzamba II, which has approximately one third of the health zone's cases, will have the latest expected year for EoT. We find that fitting the analogous deterministic version of the gHAT model using MCMC has substantially faster computation times than fitting the stochastic model using pMCMC, but produces virtually indistinguishable posterior parameterisation. This suggests that expanding health area fitting, to cover more of the DRC, should be done with deterministic fits for efficiency, but with stochastic projections used to capture both the parameter and stochastic variation in case reporting and elimination year estimations.

A simple and economic protocol for efficient in vitro fertilization using cryopreserved mouse sperm.

The advent of genome editing tools like CRISPR/Cas has substantially increased the number of genetically engineered mouse models in recent years. In support of refinement and reduction, sperm cryopreservation is advantageous compared to embryo freezing for archiving and distribution of such mouse models. The in vitro fertilization using cryopreserved sperm from the most widely used C57BL/6 strain has become highly efficient in recent years due to several improvements of the procedure. However, purchase of the necessary media for routine application of the current protocol poses a constant burden on budgetary constraints. In-house media preparation, instead, is complex and requires quality control of each batch. Here, we describe a cost-effective and easily adaptable approach for in vitro fertilization using cryopreserved C57BL/6 sperm. This is mainly achieved by modification of an affordable commercial fertilization medium and a step-by-step description of all other necessary reagents. Large-scale comparison of fertilization rates from independent lines of genetically engineered C57BL/6 mice upon cryopreservation and in vitro fertilization with our approach demonstrated equal or significantly superior fertilization rates to current protocols. Our novel SEcuRe (Simple Economical set-up for Rederivation) method provides an affordable, easily adaptable and harmonized protocol for highly efficient rederivation using cryopreserved C57BL/6 sperm for a broad application of colony management in the sense of the 3Rs.

Bayesian inference assessment of protein secondary structure analysis using circular dichroism data - how much structural information is contained in protein circular dichroism spectra?

Circular dichroism spectroscopy is an important tool for determining the structural characteristics of biomolecules, particularly the secondary structure of proteins. In this paper we propose a Bayesian model that estimates the covariance structure within a measured spectrum and quantifies the uncertainty associated with the inferred secondary structures and characteristic spectra associated with each secondary structure type. Furthermore, we used tools from Bayesian model selection to determine the best secondary structure classification scheme and illustrate a technique for comparing whether or not two or more measured protein spectra share the same secondary structure. Our findings suggest that it is not possible to identify more than 3 distinct secondary structure classes from CD spectra above 175 nm. The inclusion of data from wavelengths between 175 and 200 nm did not substantially affect the ability to determine secondary structure fractions.

Scalable Bayesian Inference for Coupled Hidden Markov and Semi-Markov Models.

Bayesian inference for coupled hidden Markov models frequently relies on data augmentation techniques for imputation of the hidden state processes. Considerable progress has been made on developing such techniques, mainly using Markov chain Monte Carlo (MCMC) methods. However, as the dimensionality and complexity of the hidden processes increase some of these methods become inefficient, either because they produce MCMC chains with high autocorrelation or because they become computationally intractable. Motivated by this fact we developed a novel MCMC algorithm, which is a modification of the forward filtering backward sampling algorithm, that achieves a good balance between computation and mixing properties, and thus can be used to analyze models with large numbers of hidden chains. Even though our approach is developed under the assumption of a Markovian model, we show how this assumption can be relaxed leading to minor modifications in the algorithm. Our approach is particularly well suited to epidemic models, where the hidden Markov chains represent the infection status of an individual through time. The performance of our method is assessed on simulated data on epidemic models for the spread of Escherichia coli O157:H7 in cattle. Supplementary materials for this article are available online.

Health Economic Analysis in Glaucoma.

The pressure on glaucoma services is ever-growing, and policymakers seek robust cost-effectiveness arguments in their decisions around resource allocation. The benefits of glaucoma are in preventing or delaying a future loss of vision and associated quality of life, and this expectation is quantified using a metric called utility which can be compared against other disease states. In recent clinical trials lasting up to 3 years, it has been difficult to show a difference in utility between glaucoma treatments in this limited period of time. When it comes to cost, the direct medical costs are only part of the broad range of costs that glaucoma brings to patients and communities, and the estimation of these costs can be difficult and imprecise. While the cost-effectiveness of glaucoma care, in general, is not in dispute, especially over longer time frames, the inability to measure changes in utility in shorter time frames impedes the uptake of innovations around the world. A number of approaches to improve the sensitivity and specificity of utility measurements are under investigation.

Mycorrhizal Fungi Respond to Resource Inequality by Moving Phosphorus from Rich to Poor Patches across Networks.

The world's ecosystems are characterized by an unequal distribution of resources [1]. Trade partnerships between organisms of different species-mutualisms-can help individuals cope with such resource inequality [2-4]. Trade allows individuals to exchange commodities they can provide at low cost for resources that are otherwise impossible or more difficult to access [5, 6]. However, as resources become increasingly patchy in time or space, it is unknown how organisms alter their trading strategies [7, 8]. Here, we show how a symbiotic fungus mediates trade with a host root in response to different levels of resource inequality across its network. We developed a quantum-dot-tracking technique to quantify phosphorus-trading strategies of arbuscular mycorrhizal fungi simultaneously exposed to rich and poor resource patches. By following fluorescent nanoparticles of different colors across fungal networks, we determined where phosphorus was hoarded, relocated, and transferred to plant hosts. We found that increasing exposure to inequality stimulated trade. Fungi responded to high resource variation by (1) increasing the total amount of phosphorus distributed to host roots, (2) decreasing allocation to storage, and (3) differentially moving resources within the network from rich to poor patches. Using single-particle tracking and high-resolution video, we show how dynamic resource movement may help the fungus capitalize on value differences across the trade network, physically moving resources to areas of high demand to gain better returns. Such translocation strategies can help symbiotic organisms cope with exposure to resource inequality.

Patient-reported Outcomes, Functional Assessment, and Utility Values in Glaucoma.

In clinical glaucoma research, the measurement of patient reported outcomes, functional assessment of disability, and health economic impact is critical. However, valid, time-efficient and comprehensive tools are not available and several current instruments lack in the appropriate precision for measuring the various dimensions of glaucoma-related quality of life (QoL), including functioning and mobility. Furthermore, statistical methods are inconsistently and sometimes incorrectly used in otherwise sound clinical studies. Standardizing and improving methods of patient-centered data collection and analysis in glaucoma studies are imperative. This paper outlines recommendations and provides a discussion of some of the pertinent issues relating to the optimization of patient-reported outcomes research in glaucoma.

An optimized electroporation approach for efficient CRISPR/Cas9 genome editing in murine zygotes.

Electroporation of zygotes represents a rapid alternative to the elaborate pronuclear injection procedure for CRISPR/Cas9-mediated genome editing in mice. However, current protocols for electroporation either require the investment in specialized electroporators or corrosive pre-treatment of zygotes which compromises embryo viability. Here, we describe an easily adaptable approach for the introduction of specific mutations in C57BL/6 mice by electroporation of intact zygotes using a common electroporator with synthetic CRISPR/Cas9 components and minimal technical requirement. Direct comparison to conventional pronuclear injection demonstrates significantly reduced physical damage and thus improved embryo development with successful genome editing in up to 100% of living offspring. Hence, our novel approach for Easy Electroporation of Zygotes (EEZy) allows highly efficient generation of CRISPR/Cas9 transgenic mice while reducing the numbers of animals required.

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study.

PURPOSE: To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. METHODS: Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire - Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. RESULTS: Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243-0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. CONCLUSIONS: Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. TRANSLATIONAL RELEVANCE: The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

Assay signal as an alternative to titer for assessment of magnitude of an antidrug antibody response.

BACKGROUND: Titer methods are commonly used to characterize the magnitude of an antidrug antibody response. Assay S/N is an appealing alternative, but the circumstances under which use of signal-to-noise (S/N) is appropriate have not been well defined. RESULTS: We validated both titer and S/N-based methods for several therapeutics. S/N correlated strongly with titer both in aggregate and when examined on a per subject basis. Analysis of impact of antibody magnitude on pharmacokinetics yielded the same result using either method. Each assay demonstrated excellent precision, good linearity, and adequate drug tolerance. CONCLUSION: Under these circumstances, assay S/N is a valid alternative to titer for assessment of the magnitude of an antidrug antibody response.

Increased rostral anterior cingulate activity following positive mental imagery training in healthy older adults.

The ability to form positive mental images may be an important aspect of mental health and well-being. We have previously demonstrated that the vividness of positive prospective imagery is increased in healthy older adults following positive imagery cognitive training. The rostral anterior cingulate cortex (rACC) is involved in the simulation of future affective episodes. Here, we investigate the effect of positive imagery training on rACC activity during the imagination of novel, ambiguous scenarios vs closely matched control training. Seventy-five participants received 4 weeks of positive imagery or control training. Participants underwent a functional magnetic resonance imaging scan, during which they completed an Ambiguous Sentences Task, which required them to form mental images in response to cues describing ambiguous social events. rACC activity was positively correlated with the pleasantness ratings of images formed. Positive imagery training increased rACC and bilateral hippocampal activity compared with the control training. Here, we demonstrate that rACC activity during positive imagery can be changed by the cognitive training. This is consistent with other evidence that this training enhances the vividness of positive imagery, and suggests the training may be acting to increase the intensity and affective quality of imagery simulating the future.

Preparation and in vitro assessment of wet-spun gemcitabine-loaded polymeric fibers: Towards localized drug delivery for the treatment of pancreatic cancer.

BACKGROUND/OBJECTIVES: There has been minimal improvement in the prognosis of pancreatic cancer cases in the past 3 decades highlighting the crucial need for more effective therapeutic approaches. A drug delivery system capable of locally delivering high concentrations of chemotherapeutics directly at the site of the tumor is clearly required. The aim of this study was to fabricate and characterize the biophysical properties of gemcitabine-eluting wet-spun polymeric fibers for localized drug delivery applications. METHODS/RESULTS: Fibers spun from alginate or chitosan solutions with or without the anticancer drug gemcitabine had a uniform surface area, were internally homogeneous and ranged from 50-120 µm in diameter. Drug encapsulation ranged from 13-52%, depending on the type and concentration of polymer used. Gemcitabine displayed first-order release kinetics where 64-82% of the loaded drug was rapidly released within the first 10 h followed by a sustained release over the next 134 h. A time dependent inhibition of ex vivo tumor spheroid growth and cell viability was observed after incubation with gemcitabine-loaded fibers but not control fibers. CONCLUSION: With further development these studies could lead to the manufacture of a safe and effective delivery system designed to combat non-resectable pancreatic cancer for which currently there is minimal chance of cure.

Assessment of contamination based on trace element concentrations in Gomphus flavipes (Odonata: Insect) larvae of the Upper Tisza Region.

Odonata larvae are frequently used to assess the contamination of aquatic systems, because they tolerate a wide range of chemical and biological conditions in freshwater systems. In early 2000, the sediments of the Hungarian section of the River Tisza and the River Szamos were strongly enriched with heavy metals by an accidental mining spill. Earlier studies demonstrated higher contamination levels in the Szamos than in the Tisza, based on sediment analysis. The aim of our study was to assess the contamination in the Upper Tisza Region, along the upper reach of the Tisza, and the lower reach of the Szamos, based on the trace element concentrations of the Gomphus flavipes larvae. We collected 269 dragonfly specimens for the analyses. The Al, Ba, Cr, Cu, Fe, Mn, Pb, Sr and Zn element contents were analysed in the dragonfly larvae by microwave plasma atomic emission spectrometry (MP-AES). Significantly higher Ba and Cu concentrations were found in the dragonfly larvae of the Tisza than the Szamos. In spite of this, the Cr, Mn, Pb, Sr and Zn concentration was significantly lower in the dragonfly larvae of the Tisza than the Szamos. For all trace elements significant differences were found along the Tisza. Significant differences were also found in all trace element concentrations of dragonfly larvae among studied localities in the Szamos, except in the cases of Al and Ba. Our results demonstrated that the Szamos was more contaminated with Cr, Mn, Pb, Sr and Zn than the Tisza, but that the Tisza was more contaminated with Ba and Cu than the Szamos, based on the trace element concentrations in Gomphus flavipes larvae, which was likely to have been caused by the tributaries of the Tisza. In summary, our results indicated a continuous pollution of the Tisza and the Szamos and their tributaries.

Activity Limitation in Glaucoma: Objective Assessment by the Cambridge Glaucoma Visual Function Test.

PURPOSE: We design and evaluate a computer-based objective simulation of activity limitation related to glaucoma. METHODS: A cross-sectional study was performed involving 70 glaucoma patients and 14 controls. Mean age was 69.0 ± 10.2 years; 49 (58.3%) were male. The Cambridge Glaucoma Visual Function Test (CGVFT) was administered to all participants. Rasch analysis and criterion, convergent, and divergent validity tests assessed the psychometric properties of the CGVFT. Regression modeling was used to determine factors predictive of CGVFT person measures. Sociodemographic information, better and worse eye visual field parameters, visual acuity, contrast sensitivity, and the Rasch-analyzed Glaucoma Activity Limitation-9 (GAL-9) and Visual Function Questionnaire Utility Index (VFQUI) questionnaire responses were recorded. RESULTS: From 139 pilot CGVFT items, 59 had acceptable fit to the Rasch model, with acceptable precision (person separation index, 2.13) and targeting. Cambridge Glaucoma Visual Function Test person measure (logit) scores increased between controls (-0.20 ± 0.08) and patients with mild (-0.15 ± 0.08), moderate (-0.13 ± 0.10), and severe (-0.05 ± 0.10) glaucoma (P < 0.001, ANOVA) indicating good criterion validity. Correlation coefficients of 0.455 (P < 0.001) between CGVFT and GAL-9 person measures and 0.399 (P = 0.005) between CGVFT and VFQUI person measures demonstrated convergent validity. Divergent validity was suboptimal. On multivariable analysis, lower better eye mean deviation and greater age were associated with worsening CGVFT person measures (P ≤ 0.001). CONCLUSIONS: The CGVFT is a computerized visual challenge test administered to a cohort of glaucoma patients. It may benefit glaucoma patients, careers, health care providers, and policy makers, providing increased awareness of activity limitation due to glaucoma.

Beyond viral suppression of HIV - the new quality of life frontier.

BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. CONCLUSIONS: Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities.

Effect-based assessment of persistent organic pollutant and pesticide dumpsite using mammalian CALUX reporter cell lines.

A combined chemical and biological analysis of samples from a major obsolete pesticide and persistent organic pollutant (POP) dumpsite in Northern Tajikistan was carried out. The chemical analytical screening focused on a range of prioritized compounds and compounds known to be present locally. Since chemical analytics does not allow measurements of hazards in complex mixtures, we tested the use of a novel effect-based approach using a panel of quantitative high-throughput CALUX reporter assays measuring distinct biological effects relevant in hazard assessment. Assays were included for assessing effects related to estrogen, androgen, and progestin signaling, aryl hydrocarbon receptor-mediated signaling, AP1 signaling, genotoxicity, oxidative stress, chemical hypoxia, and ER stress. With this panel of assays, we first quantified the biological activities of the individual chemicals measured in chemical analytics. Next, we calculated the expected sum activity by these chemicals in the samples of the pesticide dump site and compared the results with the measured CALUX bioactivity of the total extracts of these samples. The results showed that particularly endocrine disruption-related effects were common among the samples. This was consistent with the toxicological profiles of the individual chemicals that dominated these samples. However, large discrepancies between chemical and biological analysis were found in a sample from a burn place present in this site, with biological activities that could not be explained by chemical analysis. This is likely to be caused by toxic combustion products or by spills of compounds that were not targeted in the chemical analysis.

Overview and expert assessment of off-label use of misoprostol in obstetrics and gynaecology: review and report by the Collège national des gynécologues obstétriciens français.

The literature suggests that misoprostol can be offered to patients for off-label use as it has reasonable efficacy, risk/benefit ratio, tolerance and patient satisfaction, according to the criteria for evidence-based medicine. Both the vaginal and sublingual routes are more effective than the oral route for first-trimester cervical dilatation. Vaginal misoprostol 800µg, repeated if necessary after 24 or 48h, is a possible alternative for management after early pregnancy failure. However, misoprostol has not been demonstrated to be useful for the evacuation of an incomplete miscarriage, except for cervical dilatation before vacuum aspiration. Oral mifepristone 200mg, followed 24-48h later by vaginal, sublingual or buccal misoprostol 800µg (followed 3-4h later, if necessary, by misoprostol 400µg) is a less efficacious but less aggressive alternative to vacuum aspiration for elective or medically-indicated first-trimester terminations; this alternative becomes increasingly less effective as gestational age increases. In the second trimester, vaginal misoprostol 800-2400µg in 24h, 24-48h after at least 200mg of mifepristone, is an alternative to surgery, sulprostone and gemeprost. Data for the third trimester are sparse. For women with an unripe cervix and an unscarred uterus, vaginal misoprostol 25µg every 3-6h is an alternative to prostaglandin E2 for cervical ripening at term for a live fetus. When oxytocin is unavailable, misoprostol can be used after delivery for prevention (sublingual misoprostol 600µg) and treatment (sublingual misoprostol 800µg) of postpartum haemorrhage. The use of misoprostol to promote cervical dilatation before diagnostic hysteroscopy or surgical procedures is beneficial for premenopausal women but not for postmenopausal women. Nonetheless, in view of the side effects of misoprostol, its use as a first-line treatment is not indicated, and it should be reserved for difficult cases. Misoprostol is not useful for placing or removing the types of intra-uterine devices used in Europe, regardless of parity.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

BACKGROUND: Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. MATERIALS AND METHODS: FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. TRIAL STATUS: Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. TRIAL REGISTRATION: Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237.