The ETTAA study protocol: a UK-wide observational study of 'Effective Treatments for Thoracic Aortic Aneurysm'.

Introduction Chronic thoracic aortic aneurysm (CTAA) affecting the arch or descending aorta is an indolent but life-threatening condition with a rising prevalence as the UK population ages. Treatment may be in the form of open surgical repair (OSR) surgery, endovascular stent grafting (ESG) or best medical therapy (BMT). Currently, there is no consensus on the best management strategy, and no UK-specific economic studies that assess outcomes beyond the chosen procedure, but this is required in the context of greater demand for treatment and limited National Health Service (NHS) resources. Methods and analysis This is a prospective, multicentre observational study with statistical and economic modelling of patients with CTAA affecting the arch or descending aorta. We aim to gain an understanding of how treatments are currently chosen, and to determine the clinical effectiveness and cost-effectiveness of the three available treatment strategies (BMT, ESG and OSR). This will be achieved by: (1) following consecutive patients who are referred to the teams collaborating in this proposal and collecting data regarding quality of life (QoL), medical events and hospital stays over a maximum of 5 years; (2) statistical analysis of the comparative effectiveness of the three treatments; and (3) economic modelling of the comparative cost-effectiveness of the three treatments. Primary study outcomes are: aneurysm growth, QoL, freedom from reintervention, freedom from death or permanent neurological injury, incremental cost per quality-adjusted life year gained. Ethics and dissemination The study will generate an evidence base to guide patients and clinicians to determine the indications and timing of treatment, as well as informing healthcare decision-makers about which treatments the NHS should provide. The study has achieved ethical approval and will be disseminated primarily in the form of a Health Technology Assessment monograph at its completion

Retention of perampanel in adults with pharmacoresistant epilepsy at a single tertiary care center

RATIONALE: Observational data on antiepileptic drugs (AEDs) inform about their use in clinical practice. We describe our clinical experience with perampanel (PER) in a large UK tertiary epilepsy center. METHODS: Adults initiated on PER between October 2012 and March 2015 were followed until they discontinued PER or 10 September 2016. Data on epilepsy syndrome, duration, seizure types, concomitant and previous AED use, PER dosing, efficacy and side effects were recorded. Efficacy was categorized as temporary or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefit (e.g. No convulsions or daytime seizures). These categories were mutually exclusive except for people with temporary seizure freedom. RESULTS: 391 received a PER prescription, five of whom never took it. No follow-up data were available for ten. 83% had focal epilepsy. People were prescribed PER in addition to 1-7 (Interquartile range [IQR] 2, 2, 3) AEDs and had previously used up to 18 (IQR 5, 7, 10) AEDs. Total exposure was 639patient/years. Retention rates were 60.4% at one year, 48.3% at two years, and 42.7% at three years. 19 (5%) people reported seizure free periods lasting at least six months. A ≥50% reduction in seizures lasting at least six months was reported by 76 people (20%), and marked improvement for ≥6months was seen in 52 (14%). Five (1%) were taken off other AEDs and continued on PER monotherapy for 4-27months. Seizures were aggravated in 57 (15%). Somatic side effects were reported by 197 (52%), mostly CNS. Mood changes, irritability or challenging behavior were reported by 137 (36%). PER was discontinued by 211 (56%) due to adverse effects (39%), inefficacy (26%), or both (35%). No idiosyncratic adverse events were seen. CONCLUSION: PER resulted in some benefit in 40% of those exposed. Adverse effects on mental health and on balance were common and should be discussed with people before initiating PER

Characterising the incidence and mode of visceral stent failure after fenestrated endovascular aneurysm repair (FEVAR).

BackgroundIn FEVAR, visceral stents provide continuity and maintain perfusion between the main body of the stent and the respective visceral artery. The aim of this study was to characterise the incidence and mode of visceral stent failure (type Ic endoleak, type IIIa endoleak, stenosis/kink, fracture, crush and occlusion) after FEVAR in a large cohort of patients at a high-volume centre.MethodsA retrospective review of visceral stents placed during FEVAR over 15 years (February 2003-December 2018) was performed. Kaplan-Meier analyses of freedom from visceral stent-related complications were performed. The outcomes between graft configurations of varying complexity were compared, as were the outcomes of different stent types and different visceral vessels.ResultsVisceral stent complications occurred in 47/236 patients (19.9%) and 54/653 stents (8.3%). Median follow up was 3.7 years (IQR 1.7-5.3 years). There was no difference in visceral stent complication rate between renal, SMA and coeliac arteries. Visceral stent complications were more frequent in more complex grafts compared to less complex grafts. Visceral stent complications were more frequent in uncovered stents compared to covered stents. Visceral stent-related endoleaks (type Ic and type IIIa) occurred exclusively around renal artery stents. The most common modes of failure with SMA stents were kinking and fracture, whereas with coeliac artery stents it was external crush.ConclusionVisceral stent complications after FEVAR are common and merit continued and close long-term surveillance. The mode of visceral stent failure varies across the vessels in which the stents are located

The safety of device registries for endovascular abdominal aortic aneurysm repair: systematic review and meta-regression

Objectives New and re-designed stent grafts for endovascular aortic aneurysm repair (EVAR) are released regularly. Manufacturers use data from registries to assess stent graft performance, but little is known about the ability of such registries to detect rates of clinically relevant complications. The aim of this paper was to perform a systematic review and meta-analysis to determine pooled failure rates for EVAR stent grafts, to define an acceptable non-inferiority limit for these devices, and then to calculate the number of patients needed for a new device to achieve non-inferiority against published devices. Data sources and review methods MEDLINE and EMBASE were searched for studies reporting outcomes of specific EVAR grafts being used for intact infrarenal abdominal aortic aneurysms, from inception to November 2016. Meta-regression was performed to pool data and calculate the patient numbers needed to detect non-inferiority of a future graft performance. An expert consensus was performed to define adequate standards for device safety. Results One hundred and forty-seven moderate quality papers involving 27,058 patients were included. Multiple outcomes were pooled. Of these, the estimated rate (±standard error) of overall endoleak (excluding Type II) at 2 years was 5.7 ± 0.6%. The pooled re-intervention rate was 11.1 ± 0.7% at 2 years. There were differences in pooled endoleak rates between different stent graft types. Expert consensus defined non-inferiority as better performance than the worst performing 25% of stent grafts. The most popular outcome in the expert consensus was cumulative endoleak rate (excluding Type II). The number of patients who would need to be enrolled in a registry to demonstrate non-inferiority at this level was 525. Only two of 147 included studies achieved this. The second most popular choice in the expert consensus was re-intervention rate; 492 patients are required to demonstrate this. Conclusions Five hundred and twenty-five patients need to be entered into a registry to demonstrate non-inferiority to previous stent grafts. Almost all previous publications have captured lower patient numbers. With performance varying between devices, and new devices being introduced regularly, there is an urgent need to capture higher quality long-term data on EVAR stent grafts

A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms-the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol.

Funder: Health Technology Assessment Programme; Grant(s): Award ID: 15/153/02INTRODUCTION: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?' METHODS AND ANALYSIS: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years. ETHICS AND DISSEMINATION: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN85731188

Continuous Three-Dimensional Control of a Virtual Helicopter Using a Motor Imagery Based Brain-Computer Interface

Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three-dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopter's forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopter's angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications

Allelic Variation, Alternative Splicing and Expression Analysis of Psy1 Gene in Hordeum chilense Roem. et Schult

Background: The wild barley Hordeum chilense Roem. et Schult. is a valuable source of genes for increasing carotenoid content in wheat. Tritordeums, the amphiploids derived from durum or common wheat and H. chilense, systematically show higher values of yellow pigment colour and carotenoid content than durum wheat. Phytoene synthase 1 gene (Psy1) is considered a key step limiting the carotenoid biosynthesis, and the correlation of Psy1 transcripts accumulation and endosperm carotenoid content has been demonstrated in the main grass species. Methodology/Principal findings: We analyze the variability of Psy1 alleles in three lines of H. chilense (H1, H7 and H16) representing the three ecotypes described in this species. Moreover, we analyze Psy1 expression in leaves and in two seed developing stages of H1 and H7, showing mRNA accumulation patterns similar to those of wheat. Finally, we identify thirtysix different transcripts forms originated by alternative splicing of the 59 UTR and/or exons 1 to 5 of Psy1 gene. Transcripts function is tested in a heterologous complementation assay, revealing that from the sixteen different predicted proteins only four types (those of 432, 370, 364 and 271 amino acids), are functional in the bacterial system. Conclusions/Significance: The large number of transcripts originated by alternative splicing of Psy1, and the coexistence of functional and non functional forms, suggest a fine regulation of PSY activity in H. chilense. This work is the first analysis of H. chilense Psy1 gene and the results reported here are the bases for its potential use in carotenoid enhancement in duru