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\"Stories to delight before you say night-night! A collection of five beautifully illustrated animal adventures, perfect for sharing with little ones at bedtime\"-- Back cover.

To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. ClinicalTrials.gov 01914965.

We describe an unusual case of a young girl presenting with a large vagal schwannoma necessitating a transcervical‐mandibulotomy approach for total tumor resection. The presentation is unique due to the size of the lesion, the patient’s age, the operative approach, and molecular pathology. Vagal schwannomas are rare peripheral nerve sheath tumors arising from the vagus nerve. They are typically diagnosed in adulthood. We describe an atypical case in terms of size of the lesion, patient age, surgical approach, and molecular pathology.

The European Huntington’s Disease Network (EHDN), established in 2003, is a non-profit research network with the mission of advancing research, facilitating clinical trials, and improving clinical care in HD. EHDN creates a platform for clinicians, scientists, academics, patients, and family members to work together to achieve these goals. Membership of EHDN is open to those with an interest in/directly affected by HD; >200 European HD clinical and basic science centres and >3400 individuals are members. EHDN hosts a bi-annual plenary meeting, one of the world’s largest conferences dedicated to Huntington’s disease. Parallel sessions are dedicated to the latest scientific research, best practise in clinical care and clinical trials. EHDN Working Groups and Task Forces address key research topics, supported by the Think Tank experts with in-depth knowledge of HD and EHDN scientific activities. EHDN supports researchers with identifying grants and funding opportunities and awarding seed funds. An established fellowship exchange programme facilitates training of young HD professionals from countries where HD care and facilities are developing. EHDN offers review of clinical trial and study protocols, with endorsement given for protocols of high scientific and ethical quality. This statement of endorsement is valued within the HD community as an independent expert opinion. Clinical data and/or biosamples from the Registry study are available to researchers. The EHDN is governed by an Executive Committee, responsible for overseeing activities and establishing scientific strategy, and a Scientific Bioethical Advisory Committee responsible for advising on research proposals and clinical trial protocols. EHDN Central Coordination manages network operations, with regional Language Area Coordinators as the bridge between the EHDN and the clinical centres, liaising with the HD patient and research community and monitoring Enroll-HD study and platform study data. EHDN is supported by the CHDI Foundation and collaborates closely with CHDI and the Enroll-HD platform. www.ehdn.org

The European Huntington’s Disease Network (EHDN), established in 2003, is a non-profit research network with the mission of advancing research, facilitating conduct of clinical trials, and improving clinical care in HD. EHDN forms a platform for clinicians, scientists, academics, patients, and family members to work together to achieve these goals.The EHDN offers membership to those with an interest in/directly affected by HD; >200 European HD clinical and basic science centres and >3400 individuals are members.EHDN hosts a bi-annual plenary meeting, one of the world’s largest conferences dedicated to Huntington’s disease. A fellowship exchange programme has been established, to facilitate training of young HD professionals from countries where HD care and facilities are developing.The EHDN is governed by an Executive Committee, responsible for overseeing activities and establishing scientific strategy, with a Scientific Bioethical Advisory Committee responsible for reviewing research proposals. EHDN Central Coordination manages network operations, with regional Language Area Coordinators as the bridge between the EHDN and the clinical centres, liaising with the HD patient and research community and monitoring Enroll-HD study and platform data.EHDN offers review of clinical trial and study protocols, with endorsement given for protocols of high scientific and ethical quality. This statement of endorsement is valued within the HD community.EHDN Working Groups and Task Forces address key HD research topics, supported by the Think Tank, experts with in-depth knowledge of EHDN scientific activities. EHDN supports researchers with identifying grant and funding opportunities and by awarding seed funds. Clinical data and/or biosamples from the Registry study are available to researchers (see EHDN Scientific Support poster).EHDN is supported by the CHDI Foundation and collaborates closely with CHDI and the Enroll-HD platform.www.ehdn.org

ObjectivesTo present our case series and management of Scedosporium apiospermum infections of the middle ear and mastoid, and review the current literature on this rare yet potentially life-threatening condition.MethodsMedical records of patients treated at the Royal Victorian Eye and Ear Hospital for S apiospermum middle ear and mastoid infections between 2009 and 2019 were reviewed. A literature search was conducted using PubMed, Medline and Cochrane Library databases.ResultsTwo patients were identified in our institution: a 62-year-old diabetic woman with otogenic skull base osteomyelitis, and a 12-year-old boy with unilateral chronic suppurative otitis media which developed after tympanostomy tube insertion. The persistence of otalgia and otorrhoea despite prolonged antibiotic treatment characterised these cases. Both patients received voriconazole, and achieved disease resolution without complications. Ten relevant cases were identified after review of the literature. Despite treatment, there were three patient deaths, and four patients with otological or neurological complications.ConclusionThe presence of a middle ear or mastoid infection refractory to appropriate topical and systemic antibiotics should prompt clinicians to consider a fungal infection. The role of surgical debridement in the treatment of S apiospermum infection of the middle ear and mastoid is equivocal.

Sinonasal and skull base malignancies represent a rare, heterogenous group of pathologies with an incidence of 0.556 per 100,000 persons in the population. Given the numerous critical anatomic structures located adjacent to the sinonasal cavity and skull base, surgery for tumors in this region requires careful pre-operative planning with the assistance of radiological imaging and intraoperative image guidance technologies to reduce the risk of complications. Virtual surgical planning (VSP) and three-dimensional models (3DMs) are adjunctive technologies which assist clinicians to better visualize patient anatomy using enhanced digital radiological images and physical stereolithographic models based on patients’ personal imaging. This review summarizes our institutional experience with VSP and 3DMs in sinonasal and skull base surgical oncology. A clinical case series is used to thematically illustrate the application of VSP and 3DMs in surgical ablation, reconstruction, patient communication, medical education, and interdisciplinary teamwork in sinonasal and skull base surgery.

BackgroundEnroll-HD is a global observational registry study of Huntington’s disease (HD) designed to serve as a platform for clinical research. The first participant was recruited in 2012, and within less than 4 years, the study has in excess of 10 000 participants.AimsEnroll-HD is a platform designed to facilitate clinical research in Huntington’s disease.MethodsCore data are collected annually on all research participants as part of this multi-centre longitudinal observational study of Huntington’s disease. Data are monitored for quality and accuracy using a risk-based monitoring approach. All sites are required to obtain and maintain local Ethics Committee approvals.Eligible participants include gene carriers (presymptomatic and manifest) as well as individuals at risk, and controls. Assessments include core data covering motor, cognitive, and behavioural symptoms. Optional assessments include quality of life, physical functioning and work productivity measures. Phenotypic data are available for the research community at regular intervals through a straightforward downloading process, after a rigorous data monitoring process. As part of the annual assessments, Enroll-HD enables the collection of biological samples (lymphocytes, lymphoblastoid cell lines and DNA). Biological samples are also available for distribution from a central repository for clinical research.ResultsCurrently, Enroll-HD has 10 901 participants recruited from 136 sites in North America, Europe, South America and Australia/New Zealand. Clinical data and biological samples are available to researchers from 4,146 participants (presymptomatic, 21%; manifest HD, 56%, mean CAG repeat expansion: 43.0, range: 36.0; 71.0). Biological samples are available for 98.6% of study participants.ConclusionsEnroll-HD provides high quality clinical data and biological samples. As a research platform, Enroll-HD brings together a novel set of tools for HD clinical research that is easily available for researchers interested in HD and other neurodegenerative diseases.AcknowledgementsEnroll-HD is a longitudinal observational study for Huntington’s disease families intended to accelerate progress towards therapeutics; it is sponsored by CHDI Foundation, a nonprofit biomedical research organisation exclusively dedicated to developing therapeutics for HD. Enroll-HD would not be possible without the vital contribution of the research participants and their families.

BackgroundEnroll-HD is not only a study of HD; it serves as a global research platform to expedite clinical trials, understand more about the disease, and improve care. Input from clinical sites, HD families, Enroll-HD governance and lay associations has enabled a dynamic infrastructure to support and develop a host of platform activities.AimsThe Enroll-HD study is at the core of the research platform. Its clinical and biological repository of over 10,000 participants provides a rich and valuable scientific resource. Together with its established network of clinical research sites, the Enroll-HD platform is able to continue its focus on the following key aims: to accelerate the discovery and development of new therapeutics for HD, to inform our understanding of the disease, and to lead to improvements in care.Methods/techniquesEnroll-HD has a network of 136 clinical research sites. Clinical and biological samples are collected annually according to a core assessment battery. Following quality control review, data and samples are made available for wider use in the research community. Results/outcomeThe Enroll-HD platform has enabled a series of outputs for the research community:Access to data and samples: >70 approved applications for datasets and five approved requests for biosamples.Platform studiesEnroll-HD offers a range of services that can be leveraged to support platform studies, e.g., site/participant feasibility, EDC implementation, study start-up, study management and data extraction.Clinical trials- feasibilityWith a clinical research network of >130 sites, the Enroll-HD Operations team supports sites feasibility and selection for upcoming clinical trials, as well as supporting population sample feasibility.TrainingThe Enroll-HD Clinical Training Portal hosts training materials relevant to HD clinical trials and studies. ConclusionsThe platform has seen a series of successful outcomes made possible only by the collaboration of HD families, clinical and scientific research staff, lay organisations and the Enroll-HD governance committees. AcknowledgementsEnroll-HD is a longitudinal observational study for Huntington’s disease families intended to accelerate progress towards therapeutics; it is sponsored by CHDI Foundation, a nonprofit biomedical research organisation exclusively dedicated to developing therapeutics for HD. Enroll-HD would not be possible without the vital contribution of the research participants and their families.

BackgroundIn recent years there has been a significant increase in the number and size of clinical trials in HD, often competing for the same or similar patient population and HD clinical site resources. This trend is set to continue as clinical trials move into later phases of development. Enroll-HD is a global, prospective, longitudinal observational study of Huntington’s disease subjects and forms the core of the Enroll-HD research platform.AimsA key aim of the Enroll-HD study is to enhance the design and expedite the conduct of clinical trials in HD.MethodsThe Enroll-HD study is so far active in over 140 HD clinical sites in North and South America, Europe, Australia and New Zealand and has recruited over 10,900 participants including gene carriers (premanifest and manifest) as well as individuals at risk and controls. Assessments performed annually include a core data battery of motor, cognitive and behavioural symptoms in addition to the collection of socio-demographic information, medical history, co-morbid conditions and current therapies. CAG repeat values are recorded for research purposes. All participants provide written informed consent including an option to be contacted for possible future clinical research participation. Study-specific interrogation of the database enables the production of listings of potentially eligible clinical trial patients.The Enroll-HD data are monitored and sites supported by a network of regionally based HD specialist monitors and/or site managers who have longstanding relationships with the sites and are available to support study teams throughout all stages of their trials.The Enroll-HD research platform includes a developing clinical training portal intended to host training modules relevant to HD clinical trials for participating Enroll-HD site staff.ResultsThe Enroll-HD platform has so far supported 4 large global clinical trials as well as numerous smaller studies including the selection of approximately 100 HD clinical trial sites; supported the recruitment of over 800 HD patients and provided advice and troubleshooting as an integrated part of the clinical trial project management teams. A fully developed training portal will be available for future trials.AcknowledgementsEnroll-HD is a longitudinal observational study for Huntington’s disease families intended to accelerate progress towards therapeutics; it is sponsored by CHDI Foundation, a nonprofit biomedical research organisation exclusively dedicated to developing therapeutics for HD. Enroll-HD would not be possible without the vital contribution of the research participants and their families