The impact of large core and late treatment trials: An update on the modelled annual thrombectomy eligibility of UK stroke patients

\ua9 European Stroke Organisation 2024.Introduction: To support decisions about thrombectomy provision, we have previously estimated the annual UK population eligible for treatment as ∼10% of stroke admissions. Since then, eight further randomised trials that could alter the eligibility rate have reported in 2021-23. We updated our estimates of the eligible population from these trials and other recent studies. Patients and methods: An updated decision tree describing the EVT eligible population for UK stroke admissions was produced. Decision criteria were derived from the highest level of evidence available. For nodes where no specific RCT data existed, evidence was obtained from the latest systematic review(s) or the highest quality observational data. Results: We estimate that 15,420 (approximately 15%) of admitted UK stroke patients are now eligible for thrombectomy, or 14,930 if advanced brain imaging using MRI/CT perfusion or collateral assessment were used in all patients. This is a 54% increase in our previous estimate in 2021. Over 50% of LAO strokes are now potentially eligible for thrombectomy. The increase in eligibility is principally due to a much larger cohort of later presenting and/or larger ischaemic core patients. Conclusion: Most previously independent LAO stroke patients presenting within 24 h, even in the presence of a large ischaemic core on initial non-contrast CT, should be considered for thrombectomy with use of advanced brain imaging in those presenting beyond 12 h to identify salvageable penumbral brain tissue. Treatment in most patients remains critically time-dependent and our estimates should be interpreted with this in mind

Estimating the number of UK stroke patients eligible for endovascular thrombectomy

Introduction: Endovascular thrombectomy (EVT) is a highly effective treatment for acute ischemic stroke due to large arterial occlusion. Routine provision will require major changes in service configuration and workforce. An important first step is to quantify the population of stroke patients that could benefit. We estimated the annual UK population suitable for EVT using standard or advanced imaging (AI) for patient selection. Patients and Methods: Evidence from randomised control trials and national registries was combined to estimate UK stroke incidence and define a decision-tree describing the EVT eligible population. Results: Between 9,620 and 10,920 UK stroke patients (approximately 10% of stroke admissions) would be eligible for EVT annually. The majority (9,140 to 9,620) would present within 4 hours of onset and be suitable for intravenous thrombolysis. Advanced Imaging would exclude 500 patients presenting within 4 hours, but identify an additional 1,310 patients as eligible who present later. Discussion: Information from randomised control trials and large registry data provided the evidence criterion for 9 of the 12 decision points. The best available evidence was used for 2 decision-points with sensitivity analyses to determine how key branches of the tree affected estimates. Using the mid-point estimate for eligibility (9.6% of admissions) and assuming national EVT coverage, 4,280 patients would have reduced disability. Conclusion: A model combining published trials and register data suggests approximately 10% of all stroke admissions in the UK are eligible for EVT. The use of AI based on current published evidence did not have a major impact on overall numbers, but could alter eligibility status for 16% of cases

Updating estimates of the Number of UK Stroke Patients Eligible for Endovascular Thrombectomy: Incorporating Recent Evidence to Facilitate Service Planning

Introduction: Endovascular thrombectomy (EVT) is a highly effective treatment for acute ischaemic stroke due to large arterial occlusion (LAO). To support decisions about service provision, we previously estimated the annual UK population eligible for EVT as ∼10% of stroke admissions. Since then, several trials have produced evidence that could alter these figures. We update our estimates considering information from studies and trials reporting 2018–2021 on incidence, presentation time and stroke severity and consider the possible impact of predicted demographic changes in the next 10–20 years. Patients and Methods: We produce an updated decision tree describing the EVT eligible population for UK stroke admissions. One-way sensitivity analyses (using upper and lower confidence intervals for estimates at each branch of our decision tree) were used to identify where further research evidence is necessary to increase certainty around estimates for numbers of EVT eligible patients. Results: The updated estimate for the number of UK stroke patients eligible for EVT annually was between 10,020 (no advanced imaging in early presenting patients) and 9,580 (advanced imaging in all early presenting patients), which compared with our estimates in 2017 is a minimal reduction. One-way sensitivity analyses established that enhanced evidence about eligibility for milder strokes, ASPECTS scores and pre-stroke disability are offset by evidence regarding a lower incidence of LAO. Importantly, predicted increases in life expectancy by 2040 may increase thrombectomy need by 40%. Discussion: Information from additional randomised trials published during 2018–2020 with updated estimates of LAO prevalence had a minimal impact on overall estimates of stroke patients eligible for EVT in the UK. Ongoing research into the benefits of EVT for patients with mild stroke or European Stroke Journal For Peer Review lower ASPECTS scores has the potential to increase the estimates of the eligible population; future need for EVT will increase with the ageing population. Conclusion: Our updated analyses show overall numbers eligible little changed, but evidence from ongoing trials and demographic changes have the potential to increase the need for EVT significantly. Patients and Methods: We produce an updated decision-tree describing the EVT eligible population for UK stroke admissions. One-way sensitivity analyses (using upper and lower confidence intervals for estimates at each branch of our decision tree) were used to identify where further research evidence is necessary to increase certainty around estimates for numbers of EVT eligible patients. Results: The updated estimate for the number of UK stroke patients eligible for EVT annually was between 10,020 (no advanced imaging in early presenting patients) and 9,580 (advanced imaging in all early presenting patients), which compared with our estimates in 2017 is a minimal reduction. One-way sensitivity analyses established that enhanced evidence about eligibility for milder strokes, ASPECTS scores and pre-stroke disability are offset by evidence regarding a lower incidence of LAO. Importantly, predicted increases in life expectancy by 2040 may increase thrombectomy need by 40%. Discussion: Information from additional randomised trials published 2018-2020 with updated estimates of LAO prevalence had a minimal impact on overall estimates of stroke patients eligible for EVT in the UK. Ongoing research into the benefits of EVT for patients with mild stroke or lower ASPECTS scores has the potential to increase the estimates of the eligible population; future need for EVT will increase with the ageing population. Conclusion: Our updated analyses show overall numbers eligible little changed but evidence from ongoing trials and demographic changes have the potential to increase the need for EVT significantly

Elucidating the long-range charge carrier mobility in metal halide perovskite thin films

Many optoelectronic properties have been reported for lead halide perovskite polycrystalline films. However, ambiguities in the evaluation of these properties remain, especially for long-range lateral charge transport, where ionic conduction can complicate interpretation of data. Here we demonstrate a new technique to measure the long-range charge carrier mobility in such materials. We combine quasi-steady-state photo-conductivity measurements (electrical probe) with photo-induced transmission and reflection measurements (optical probe) to simultaneously evaluate the conductivity and charge carrier density. With this knowledge we determine the lateral mobility to be ~ 2 cm2/Vs for CH3NH3PbI3 (MAPbI3) polycrystalline perovskite films prepared from the acetonitrile/methylamine solvent system. Furthermore, we present significant differences in long-range charge carrier mobilities, from 2.2 to 0.2 cm2/Vs, between films of contemporary perovskite compositions prepared via different fabrication processes, including solution and vapour phase deposition techniques. Arguably, our work provides the first accurate evaluation of the long-range lateral charge carrier mobility in lead halide perovskite films, with charge carrier density in the range typically achieved under photovoltaic operation

Diagnosis of exercise-induced left bundle branch block at rest by scintigraphic phase analysis

Accurate diagnosis of diseases of the ventricular conducting system is essential for their appropriate therapy. some conduction abnormalities, such as exercise-induced left bundle branch block (EX-LBBB), are not apparent on resting electrocardiograms. Phase analysis of rest and exercise radionuclide ventriculograms (RVG's) was used to compare four EX-LBBB patients with six normal controls. All patients had normal resting electrocardiograms, ejection fractions, and visually normal wall motion. First harmonic phase images were generated reflecting the timing of ventricular contraction. Dynamic phase displays were reviewed and graded in a blinded fashion by three independent experienced observers. Phase angle histograms of the right and left ventricle were determined for both resting and exercise images. The mean phase angle and standard deviation were also calculated for each ventricle. Visual grading of the resting phase images failed to show a significant difference between normal patients and patients with EX-LBBB. Quantitative analysis, however, revealed a significant difference in mean phase angle differences (LV-RV) in resting studies: 0.8° (±1.9° SEM) in normals versus 9.3° (±2.3° SEM) in EX-LBBB patients ( P <0.03). Exercise accentuated the phase angle differences: 1.8° in normals vs. 31.2° in EX-LBBB patients ( P <0.001). Quantitative phase analysis of resting RVG's permits the diagnosis of cardiac conduction disease that is not apparent on the resting EKG and may result in better monitoring and treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46821/1/259_2004_Article_BF00261005.pd

Estimating the effectiveness and cost-effectiveness of establishing additional endovascular Thrombectomy stroke Centres in England::a discrete event simulation

Background We have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30. Methods We constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year’s incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30. Results Of 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters (< 270 min since onset) would reduce from 195 (IQR 155–249) to 165 (IQR 105–224) minutes. Our model predicts reconfiguration would mean an additional 33 independent patients (modified Rankin scale [mRS] 0–1) and 30 fewer dependent/dead patients (mRS 3–6) per year. The net addition of 6 centres generates 190 QALYs (95%CI − 6 to 399) and results in net savings to the healthcare system of £1,864,000/year (95% CI -1,204,000 to £5,017,000). The estimated budget impact was a saving of £980,000 in year 1 and £7.07 million in years 2 to 5. Conclusion Changes in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required

A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: A Gynecologic Oncology Group Study

Nab-paclitaxel is a novel Cremophor®-free nanoparticle of albumin-stabilized paclitaxel, which has favorable efficacy and toxicity characteristics relative to other solvent-based taxanes, such as paclitaxel and docetaxel

Back-contact perovskite solar cell fabrication via microsphere lithography

Back-contact electrodes for hybrid organic-inorganic perovskite solar cells (PSCs) eliminate the parasitic absorption losses caused by the transparent conductive electrodes that are inherent to conventional sandwich-architecture devices. However, the fabrication methods for these unconventional architectures rely heavily on expensive photolithography, which limits scalability. Herein, we present an alternative cost-effective microfabrication technique in which the conventional photolithography process is replaced by microsphere lithography in which a close-packed polystyrene microsphere monolayer acts as the patterning mask for the honeycomb-shaped electrodes. A comprehensive comparison between photolithography and microsphere lithography fabrication techniques was conducted. Using microsphere lithography, we achieve highly efficient devices having a stabilized power conversion efficiency (PCE) of 8.6%, twice the reported value using photolithography. Microsphere lithography also enabled the fabrication of the largest back-contact PSC to date, having an active area of 0.75 cm2 and a stabilized PCE of 2.44%.This work was financially supported by the Australian Government through the Australian Renewable Energy Agency (ARENA) the Australian Centre for Advanced Photovoltaics (ACAP) and the Australian Research Council (ARC, DE220100154). This work was performed in part at the Melbourne Centre for Nanofabrication (MCN) in the Victorian Node of the Australian National Fabrication Facility (ANFF). The authors acknowledge use of facilities within the Monash Centre for Electron Microscopy (MCEM). The authors acknowledge use of facilities within the Flexible Electronics Laboratory (FEL) at the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Clayton site. S.R.R. acknowledges the support from “la Caixa” Foundation (ID 100010434). Fellowship code LCF/BQ/PI20/11760024.Peer reviewe

Naphthalene-imide Self-assembled Monolayers as a Surface Modification of ITO for Improved Thermal Stability of Perovskite Solar Cells [Dataset]

38 pages. -- 1. Thermal Properties. -- 2. Cyclic Voltammetry. -- 3. Optical Characterization. -- 4. Energy Level Diagram. -- 5. Self-Assembly. -- 6. Water Contact Angle Measurements. -- 7. XPS Measurements. -- 8. Perovskite Solar Cells. -- 9. Surface Recombination Velocity Measurements. -- 10. Drift-Diffusion Simulations. -- 11. Shelf-Life Stability. -- 12. Synthesis. -- 12.1. Naphthalene monoimides 2a-2d. -- 12.2. Naphthalene diimides 3a-3d. -- 13. ReferencesElectron-transport-layer-free (ETL-free) perovskite solar cells (PSCs) show great promise for commercialization due to their simple design and ease of fabrication. However, the interface between the transparent conductive oxides such as indium-doped tin oxide (ITO) and the perovskite is not optimal due to differences in their work functions, surface defects, and wettability of the substrates. Surface modification of ITO through self-assembled monolayers (SAMs) to get ITO/SAM charge selective layers has shown great improvement in device performance in recent years, but little emphasis has been put on the stability of these devices. Here, we address this gap by introducing a series of newly synthesized naphthalene-imide derivatives which self-assemble at the interface between ITO and the perovskite interface and study their impact on the thermal stability of triple-cation PSCs. The chemical and thermal stabilities of the naphthalene-imide SAMs help improve the thermal stability of the devices, reaching T80 lifetimes exceeding 800 h for devices containing a pyridine-functionalized naphthalene diimide carboxylic acid at 85 °C in air. In addition, all SAMs improve the stabilized power output of the devices with respect to ITO-only reference devices. Drift-diffusion simulations reveal the strong influence of the ITO work function on the efficiency in ETL-free devices, and a work function reduction of 0.2 eV could improve efficiencies by over 30%. The functional diversity of naphthalene imides coupled with the ease of SAM deposition opens a pathway for stable, high-performing PSCs based on electron selective monolayers.Peer reviewe