Update to the study protocol Face Your Fears:Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial

We unfortunately need to make an update to our published study protocol that describes a significant change in the design of the study. The Committee on Health Research Ethics of the Capital Region Denmark recently rejected the approval of changing the primary outcome in the trial, on the invariable grounds that the trial has already commenced. It is therefore necessary to retain the Green Paranoid Thought Scale (GPTS) part B, ideas of persecution, as our primary outcome, and GPTS part A, ideas of social reference, as a secondary outcome, which is described opposite in our published study protocol. The exchange of outcomes has not affected participation in our trial or the informed consent. Intervention in both groups and assessments are unchanged. The two outcomes together constitute GPTS and the unifying concept we attempt to treat, namely paranoid ideations. As this is a blinded, methodologically rigorous trial, we did not have—and still do not have—access to preliminary data, and therefore, we have no knowledge of the distribution of our two intervention groups nor the potential effect of the intervention. The power calculation remains unchanged irrespective of the selection of the primary outcome. We have been fully transparent with the changes in primary and secondary outcomes on ClinicalTrials.gov throughout the trial. Due to the considerations mentioned above, we assumed that there would not be any ethical implications of the change of primary outcome. We sincerely apologize for the irregularity caused because of this assumption. Trial registration: ClinicalTrials.gov NCT04902066. Initial release April 19th, 2021.</p

CHALLENGE and Face Your Fears: Virtual Reality Treatment for Auditory Hallucinations and Paranoid Ideations

Background: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations and paranoid ideations despite receiving current treatment. Virtual reality assisted treatment offers the potential of advancing current psychotherapies for psychotic symptoms by creating virtual environments that can elicit responses (e.g. thoughts, feelings, behaviours) mirroring real-world settings. In two large-scale randomised clinical trials, we are investigating whether targeted virtual reality assisted psychotherapy can reduce psychotic symptoms and increase daily life functioning and quality of life. The CHALLENGE trial examines whether nine sessions of virtual reality-assisted psychotherapy is superior to nine sessions of standard treatments in reducing the severity, frequency, and distress of auditory hallucinations in patients with psychosis. In the Face your Fears trial we are investigating whether virtual reality assisted cognitive behavioral therapy (CBT) is superior to standard CBT in reducing levels of paranoid ideation in patients with psychosis spectrum disorders. Methods: The CHALLENGE and Face your Fears trials are randomised, assessor-blinded parallel-groups superiority clinical trials, allocating a total of 266 and 256 patients, respectively to either the experimental intervention or a control condition. The trials are currently enrolling patients; thus, no quantitative data is available yet. The main objective of this presentation is to give a qualitative account of this new psychotherapeutic methods as it is applied in both trials. Results: Qualitative data comprising case descriptions and video material will be presented at the conference. Discussion: The preliminary findings indicate great potential for these innovative treatments albeit important concerns regarding implementation will be raised. DISCLOSURE: No significant relationships

Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders:a randomized clinical trial

Background: Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral therapy (CBT) for psychosis show small to moderate effect sizes in reducing paranoid ideations. Virtual reality-based CBT (VR-CBT) could improve therapy efficacy as exposure and behavioral experiments in VR can be optimized, individualized, and carried out in a safe environment. Few VR-CBT studies exist for paranoid ideations and there is a need for large-scale, methodologically rigorous trials. Methods: This study is a randomized, assessor-blinded parallel-groups multi-center superiority clinical trial, fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients diagnosed with schizophrenia spectrum disorder, including schizotypal disorder (ICD-10 F20-29), will be allocated to either 10 sessions of symptom-specific CBT-VR plus treatment as usual-versus 10 sessions of standard symptom-specific CBT for paranoid ideations (CBT) plus treatment as usual. All participants will be assessed at baseline, treatment end (3 months post baseline), and then 9 months post baseline. A stratified block-randomization with concealed randomization sequence will be conducted. Independent assessors blinded to the treatment will evaluate the outcome. Analysis of outcome will be carried out with the intention to treat principles. The primary outcome is ideas of social reference measured with Green Paranoid Thought Scale Part A (GPTS-A) at the cessation of treatment at 3 months post baseline. Secondary outcomes are ideas of persecution (GPTS-B), Social Interaction Anxiety Scale (SIAS), Personal and Social Performance scale (PSP), Safety Behavior Questionnaire (SBQ), and CANTAB Emotion Recognition Task. Discussion: The trial will elucidate whether VR-CBT can enhance therapy efficacy for paranoid ideations. Additionally, Trial findings will provide evidence on the effectiveness and cost-effectiveness of VR-CBT for paranoid ideations that can guide the possible dissemination and implementation into clinical practice

Indoor Radon Concentration and Risk Estimation: the EURA PROJECT

The indoor radon concentration level has been monitored in selected locations in four European countries (Iceland, Italy, Norway, and Sweden) during a yearlong measurement campaign using time-integrated passive radon dosimeters containing CR-39 track detectors. The measurements were carried out in private houses and public buildings like schools, for an exposure time of up to 6 months for each detector. Experimental data shows a great variation between different geographic areas, and often the average levels are over the acceptable radon limit of 300 Bq/m3recommended by the International Commission on Radiological Protection (ICRP). To investigate a relationship between indoor radon exposure and lung cancer, estimating the cumulative levels of exposure to indoor radon for an individual or population is necessary. We analyse the data sets and investigate the factors influencing indoor radon concentrations in order to determine the best use of the experimental information. The results show that the variables associated with indoor radon levels are strictly linked to the soil geology. Analyzing the data sets enables improved assessment of radon exposure in a given area. The average absorption effective dose equivalent for a person is computed, and the risk of lung cancer per year is evaluated. Doi: 10.28991/HEF-2021-02-04-01 Full Text: PD

Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis

publishedVersio

A Photo Score for Aesthetic Outcome in Sagittal Synostosis:An ERN CRANIO Collaboration

European Reference Network (ERN) CRANIO is focused on optimizing care for patients with rare or complex craniofacial anomalies, including craniosynostosis and/or rare ear, nose, and throat disorders. The main goal of ERN CRANIO is to collect uniform data on treatment outcomes for multicenter comparison. We aimed to develop a reproducible and reliable suture-specific photo score that can be used for cross-center comparison of phenotypical severity of sagittal synostosis and aesthetic outcome of treatment. We conducted a retrospective study among nonsyndromic sagittal synostosis patients aged &lt;19 years. We included preoperative and postoperative photo sets from 6 ERN CRANIO centers. Photo sets included bird's eye, lateral, and anterior-posterior views. The sagittal synostosis photo score was discussed in the working group, and consensus was obtained on its contents. Interrater agreement was assessed with weighted Fleiss' Kappa and intraclass correlation coefficients.The photo score consisted of frontal bossing, elongated skull, biparietal narrowness, temporal hollowing, vertex line depression, occipital bullet, and overall phenotype. Each item was scored as normal, mild, moderate, or severe. Results from 36 scaphocephaly patients scored by 20 raters showed kappa values ranging from 0.38 [95% bootstrap CI: 0.31, 0.45] for biparietal narrowness to 0.56 [95% bootstrap CI: 0.47, 0.64] for frontal bossing. Agreement was highest for the sum score of individual items [intraclass correlation coefficients agreement 0.69 [95% CI: 0.57, 0.82]. This is the first large-scale multicenter study in which experts investigated a photo score to assess the severity of sagittal synostosis phenotypical characteristics. Agreement on phenotypical characteristics was suboptimal (fair-moderate agreement) and highest for the summed score of individual photo score items (substantial agreement), indicating that although experts interpret phenotypical characteristics differently, there is consensus on overall phenotypical severity.</p

Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. Results: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.Peer reviewe

Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.ope