Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

Cost-effectiveness of CT perfusion for the detection of large vessel occlusion acute ischemic stroke followed by endovascular treatment: a model-based health economic evaluation study.

OBJECTIVES: CT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)-eligible occlusion detection using model-based analyses. METHODS: In this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018-March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT + CTA + CTP) with a generated counterfactual where NCCT and CTA (NCCT + CTA) was used for LVO detection. The NCCT + CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (ΔQALY) and costs (ΔCosts) per LVO patient. RESULTS: We included 701 patients (median age: 72, IQR: [62-81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (ΔCosts median: € - 2671, IQR: [€ - 4721; € - 731]), a health gain (ΔQALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient. CONCLUSION: CTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective. CLINICAL RELEVANCE STATEMENT: Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective. KEY POINTS: • Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up. • Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: € - 3857, IQR: [€ - 5907; € - 1916] per patient). • As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required.

Costs and health effects of CT perfusion-based selection for endovascular thrombectomy within 6 hours of stroke onset: a model-based health economic evaluation.

BACKGROUND: Although CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient selection for endovascular treatment (EVT) in patients presenting within 6 hours after symptom onset with a large vessel occlusion. METHODS: Patients with a large vessel occlusion were included from a Dutch nationwide cohort (n=703) if CTP imaging was performed before EVT within 6 hours after stroke onset. Simulated cost and health effects during 5 and 10 years follow-up were compared between CTP based patient selection for EVT and providing EVT to all patients. Outcome measures were the net monetary benefit at a willingness-to-pay of €80 000 per quality-adjusted life year, incremental cost-effectiveness ratio), difference in costs from a healthcare payer perspective (ΔCosts) and quality-adjusted life years (ΔQALY) per 1000 patients for 1000 model iterations as outcomes. RESULTS: Compared with treating all patients, CTP-based selection for EVT at the optimised ischaemic core volume (ICV≥110 mL) or core-penumbra mismatch ratio (MMR≤1.4) thresholds resulted in losses of health (median ΔQALYs for ICV≥110 mL: -3.3 (IQR: -5.9 to -1.1), for MMR≤1.4: 0.0 (IQR: -1.3 to 0.0)) with median ΔCosts for ICV≥110 mL of -€348 966 (IQR: -€712 406 to -€51 158) and for MMR≤1.4 of €266 513 (IQR: €229 403 to €380 110)) per 1000 patients. Sensitivity analyses did not yield any scenarios for CTP-based selection of patients for EVT that were cost-effective for improving health, including patients aged ≥80 years CONCLUSION: In EVT-eligible patients presenting within 6 hours after symptom onset, excluding patients based on CTP parameters was not cost-effective and could potentially harm patients.

Cost-effectiveness of tenecteplase versus alteplase for stroke thrombolysis evaluation trial in the ambulance.

BACKGROUND: Tenecteplase administered to patients with ischaemic stroke in a mobile stroke unit (MSU) has been shown to reduce the perfusion lesion volumes and result in ultra-early recovery. We now seek to assess the cost-effectiveness of tenecteplase in the MSU. METHODS: A within-trial (TASTE-A) economic analysis and a model-based long-term cost-effectiveness analysis were performed. This post hoc within-trial economic analysis utilised the patient-level data (intention to treat, ITT) prospectively collected over the trial to calculate the difference in both healthcare costs and quality-adjusted life years (QALYs, estimated from modified Rankin scale score). A Markov microsimulation model was developed to simulate the long-term costs and benefits. RESULTS: In total, there were 104 patients with ischaemic stroke randomised to tenecteplase (n = 55) or alteplase (n = 49) treatment groups, respectively in the TASTE-A trial. The ITT-based analysis showed that treatment with tenecteplase was associated with non-signficantly lower costs (A$28,903 vs A$40,150 (p = 0.056)) and greater benefits (0.171 vs 0.158 (p = 0.457)) than that for the alteplase group over the first 90 days post the index stroke. The long-term model showed that tenecteplase led to greater savings in costs (-A$18,610) and more health benefits (0.47 QALY or 0.31 LY gains). Tenecteplase-treated patients had reduced costs for rehospitalisation (-A$1464), nursing home care (-A$16,767) and nonmedical care (-A$620) per patient. CONCLUSIONS: Treatment of ischaemic stroke patients with tenecteplase appeared to be cost-effective and improve QALYs in the MSU setting based on Phase II data. The reduced total cost from tenecteplase was driven by savings from acute hospitalisation and reduce need for nursing home care.

Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients: The Stentrode With Thought-Controlled Digital Switch (SWITCH) Study.

Importance: Brain-computer interface (BCI) implants have previously required craniotomy to deliver penetrating or surface electrodes to the brain. Whether a minimally invasive endovascular technique to deliver recording electrodes through the jugular vein to superior sagittal sinus is safe and feasible is unknown. Objective: To assess the safety of an endovascular BCI and feasibility of using the system to control a computer by thought. Design, Setting, and Participants: The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients' homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022. Interventions: Recording devices were delivered via catheter and connected to subcutaneous electronic units. Devices communicated wirelessly to an external device for personal computer control. Main Outcomes and Measures: The primary safety end point was device-related serious adverse events resulting in death or permanent increased disability. Secondary end points were blood vessel occlusion and device migration. Exploratory end points were signal fidelity and stability over 12 months, number of distinct commands created by neuronal activity, and use of system for digital device control. Results: Of 4 patients included in analyses, all were male, and the mean (SD) age was 61 (17) years. Patients with preserved motor cortex activity and suitable venous anatomy were implanted. Each completed 12-month follow-up with no serious adverse events and no vessel occlusion or device migration. Mean (SD) signal bandwidth was 233 (16) Hz and was stable throughout study in all 4 patients (SD range across all sessions, 7-32 Hz). At least 5 attempted movement types were decoded offline, and each patient successfully controlled a computer with the BCI. Conclusions and Relevance: Endovascular access to the sensorimotor cortex is an alternative to placing BCI electrodes in or on the dura by open-brain surgery. These final safety and feasibility data from the first in-human SWITCH study indicate that it is possible to record neural signals from a blood vessel. The favorable safety profile could promote wider and more rapid translation of BCI to people with paralysis. Trial Registration: ClinicalTrials.gov Identifier: NCT03834857.

Cost-Effectiveness of Endovascular Treatment in Large Vessel Occlusion Stroke With Mild Prestroke Disability: Results From the HERMES Collaboration.

BACKGROUND: The clinical and economic benefit of endovascular treatment (EVT) in addition to best medical management in patients with stroke with mild preexisting symptoms/disability is not well studied. We aimed to investigate cost-effectiveness of EVT in patients with large vessel occlusion and mild prestroke symptoms/disability, defined as a modified Rankin Scale score of 1 or 2. METHODS: Data are from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), which pooled patient-level data from 7 large, randomized EVT trials. We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a health care and a societal perspective. Incremental cost-effectiveness ratio and net monetary benefits were calculated, and a probabilistic sensitivity analysis was performed. RESULTS: EVT in addition to best medical management resulted in lifetime cost savings of $2821 (health care perspective) or $5378 (societal perspective) and an increment of 1.27 quality-adjusted life years compared with best medical management alone, indicating dominance of additional EVT as a treatment strategy. The net monetary benefits were higher for EVT in addition to best medical management compared with best medical management alone both at the higher (100 000$/quality-adjusted life years) and lower (50 000$/quality-adjusted life years) willingness to pay thresholds. Probabilistic sensitivity analysis showed decreased costs and an increase in quality-adjusted life years for additional EVT compared with best medical management only. CONCLUSIONS: From a health-economic standpoint, EVT in addition to best medical management should be the preferred strategy in patients with acute ischemic stroke with large vessel occlusion and mild prestroke symptoms/disability.

Long-Term Cost-Effectiveness of Severity-Based Triaging for Large Vessel Occlusion Stroke.

Background and Purpose: Pre-hospital severity-based triaging using the Ambulance Clinical Triage For Acute Stroke Treatment (ACT-FAST) algorithm has been demonstrated to substantially reduce time to endovascular thrombectomy in Melbourne, Australia. We aimed to model the cost-effectiveness of an ACT-FAST bypass system from the healthcare system perspective. Methods: A simulation model was developed to estimate the long-term costs and health benefits associated with diagnostic accuracy of the ACT-FAST algorithm. Three-month post stroke functional outcome was projected to the lifetime horizon to estimate the long-term cost-effectiveness between two strategies (ACT-FAST vs. standard care pathways). For ACT-FAST screened true positives (i.e., screened positive and eligible for EVT), a 52 mins time saving was applied unanimously to the onset to arterial time for EVT, while 10 mins delay in thrombolysis was applied for false-positive (i.e., screened positive but was ineligible for EVT) thrombolysis-eligible infarction. Quality-adjusted life year (QALY) was employed as the outcome measure to calculate the incremental cost-effectiveness ratio (ICER) between the ACT-FAST algorithm and the current standard care pathway. Results: Over the lifetime, ACT-FAST was associated with lower costs (-$45) and greater QALY gains (0.006) compared to the current standard care pathway, resulting in it being the dominant strategy (less costly but more health benefits). Implementing ACT-FAST triaging led to higher proportion of patients received EVT procedure (30 more additional EVT performed per 10,000 patients). The total Net Monetary Benefit from ACT-FAST care estimated at A$0.76 million based on its implementation for a single year. Conclusions: An ACT-FAST severity-triaging strategy is associated with cost-saving and increased benefits when compared to standard care pathways. Implementing ACT-FAST triaging increased the proportion of patients who received EVT procedure due to more patients arriving at EVT-capable hospitals within the 6-h time window (when imaging selection is less rigorous).

Cost-effectiveness of CT perfusion for patients with acute ischemic stroke (CLEOPATRA)-Study protocol for a healthcare evaluation study.

Introduction: Computed tomography perfusion (CTP) is variably considered to assess eligibility for endovascular thrombectomy (EVT) in acute ischemic (AIS) stroke patients. Although CTP is recommended for patient selection in later (6-24 h) time window, it is currently not recommended in the earlier (0-6 h) time window and the costs and health effects of including CTP for EVT selection remain unknown. We aim to estimate the costs and health effects of using CTP for EVT selection in AIS patients compared to conventional selection. Patients and methods: CLEOPATRA is a healthcare evaluation study using clinical and imaging data from multiple, prospective EVT trials and registries in both the earlier and later time windows. To study the long-term health and cost effects, we will construct a ("Markov") health state transition model simulating the clinical outcome over a 5-year follow-up period for CTP-based and conventional selection for EVT. Clinical data acquired within the current study and estimates from the literature will be used as input for probabilities of events, costs, and Quality-Adjusted Life Years (QALYs) per modified Rankin Scale (mRS) subscore. Primary outcome for the cost-effectiveness analysis will be the Incremental Cost-Effectiveness Ratio (ICER) in terms of costs per QALY gained over the simulated follow-up period. Study outcomes: Outcome measures will be reported as cumulative values over a 5-year follow-up period. Discussion: This study will provide preliminary insight into costs and health effects of including CTP in the selection for EVT for AIS patients, presenting between 0 and 24 h after time last known well. The results may be used to develop recommendations and inform further implementation projects and studies.

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.

INTRODUCTION: 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.

Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials.

Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.

SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group.

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Predictors of Quality-of-Life Improvements Following Global Head and Neck Surgery Trips to Underserved Regions.

OBJECTIVES/HYPOTHESIS: To conduct longitudinal postoperative follow-up and discern health-related quality-of-life (HR-QoL) changes using a validated questionnaire among patients undergoing head and neck surgeries during a short-term, global surgical trip in a resource-limited setting. To identify clinicodemographic predictors of post-operative HR-QoL improvements in this setting. STUDY DESIGN: Retrospective observational study with prospective follow-up. METHODS: Patients undergoing surgery at Moi Teaching and Referral Hospital in Eldoret, Kenya through the authors' short-term surgical trip (STST) between 2016 and 2019 were asked to complete preoperative Short Form-36 (SF-36) HR-QoL questionnaires, and postoperative SF-36 questionnaires during subsequent follow-up. Preoperative and postoperative SF-36 domain scores, and two composite scores (mental component summary [MCS] and physical component summary [PCS]) were compared. Linear regression models were fit to identify clinicodemographic factors predictors of general health (GH), MCS, and PCS scores. RESULTS: Among the 26 participating patients, significant improvements were seen in post-operative GH (mean change = 19.8) and MCS (mean change = 11.2) scores. Lower pre-operative GH, MCS, and PCS scores were predictive of greater improvement in the corresponding post-operative scores. Longer time to follow-up was associated with greater improvement in GH score. Mean follow-up interval was 23.1 months (SD = 1.8 months). CONCLUSIONS: Utilizing the SF-36 questionnaire, we found that patients' perception of their general and psychosocial health improved after undergoing head and neck surgeries through a global STST. This study provides important, preliminary evidence that that elective surgeries performed in low-resource settings convey substantial benefit to patient QoL. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2006-2010, 2021.

Economic evaluation of the Melbourne Mobile Stroke Unit.

BACKGROUND: The Melbourne Mobile Stroke Unit (MSU) is the first Australian service to provide prehospital acute stroke treatment, including thrombolysis and facilitated triage for endovascular thrombectomy. AIMS: To estimate the cost-effectiveness of the MSU during the first full year of operation compared with standard ambulance and hospital stroke care pathways (standard care). METHODS: The costs and benefits of the Melbourne MSU were estimated using an economic simulation model. Operational costs and service utilization data were obtained from the MSU financial and patient tracking reports. The health benefits were estimated as disability-adjusted life years (DALYs) avoided using local data on reperfusion therapy and estimates from the published literature on their effectiveness. Costs were presented in Australian dollars. The robustness of results was assessed using multivariable (model inputs varied simultaneously: 10,000 Monte Carlo iterations) and various one-way sensitivity analyses. RESULTS: In 2018, the MSU was dispatched to 1244 patients during 200 days of operation. Overall, 167 patients were diagnosed with acute ischemic stroke, and 58 received thrombolysis, endovascular thrombectomy, or both. We estimated 27.94 DALYs avoided with earlier access to endovascular thrombectomy (95% confidence interval (CI) 15.30 to 35.93) and 16.90 DALYs avoided with improvements in access to thrombolysis (95% CI 9.05 to 24.68). The MSU was estimated to cost an additional $30,982 per DALY avoided (95% CI $21,142 to $47,517) compared to standard care. CONCLUSIONS: There is evidence that the introduction of MSU is cost-effective when compared with standard care due to earlier provision of reperfusion therapies.

Articulating the effect of food systems innovation on the Sustainable Development Goals.

Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level.

Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke.

BACKGROUND AND PURPOSE: Tenecteplase improved functional outcomes and reduced the requirement for endovascular thrombectomy in ischemic stroke patients with large vessel occlusion in the EXTEND-IA TNK randomized trial. We assessed the cost-effectiveness of tenecteplase versus alteplase in this trial. METHODS: Post hoc within-trial economic analysis included costs of index emergency department and inpatient stroke hospitalization, rehabilitation/subacute care, and rehospitalization due to stroke within 90 days. Sources for cost included key study site complemented by published literature and government websites. Quality-adjusted life-years were estimated using utility scores derived from the modified Rankin Scale score at 90 days. Long-term modeled cost-effectiveness analysis used a Markov model with 7 health states corresponding to 7 modified Rankin Scale scores. Probabilistic sensitivity analyses were performed. RESULTS: Within the 202 patients in the randomized controlled trial, total cost was nonsignificantly lower in the tenecteplase-treated patients (40 997 Australian dollars [AUD]) compared with alteplase-treated patients (46 188 AUD) for the first 90 days(P=0.125). Tenecteplase was the dominant treatment strategy in the short term, with similar cost (5412 AUD [95% CI, -13 348 to 2523]; P=0.181) and higher benefits (0.099 quality-adjusted life-years [95% CI, 0.001-0.1967]; P=0.048), with a 97.4% probability of being cost-effective. In the long-term, tenecteplase was associated with less additional lifetime cost (96 357 versus 106 304 AUD) and greater benefits (quality-adjusted life-years, 7.77 versus 6.48), and had a 100% probability of being cost-effective. Both deterministic sensitivity analysis and probabilistic sensitivity analyses yielded similar results. CONCLUSIONS: Both within-trial and long-term economic analyses showed that tenecteplase was highly likely to be cost-effective for patients with acute stroke before thrombectomy. Recommending the use of tenecteplase over alteplase could lead to a cost saving to the healthcare system both in the short and long term. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388061.

Public health and cost consequences of time delays to thrombectomy for acute ischemic stroke.

OBJECTIVE: To determine public health and cost consequences of time delays to endovascular thrombectomy (EVT) for patients, health care systems, and society, we estimated quality-adjusted life-years (QALYs) of EVT-treated patients and associated costs based on times to treatment. METHODS: The Markov model analysis was performed from US health care and societal perspectives over a lifetime horizon. Contemporary data from 7 trials within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration served as data source. Aside from cumulative lifetime costs, we calculated the net monetary benefit (NMB) to determine the economic value of care. We used a contemporary willingness-to-pay threshold of $100,000 per QALY for NMB calculations. RESULTS: Every 10 minutes of earlier treatment resulted in an average gain of 39 days (95% prediction interval 23-53 days) of disability-free life. Overall, the cumulative lifetime costs for patients with earlier or later treatment were similar. Patients with later treatment had higher morbidity-related costs but over a shorter time span due to their shorter life expectancy, resulting in similar lifetime costs as in patients with early treatment. Regarding the economic value of care, every 10 minutes of earlier treatment increased the NMB by $10,593 (95% prediction interval $5,549-$14,847) and by $10,915 (95% prediction interval $5,928-$15,356) taking health care and societal perspectives, respectively. CONCLUSIONS: Any time delay to EVT reduces QALYs and decreases the economic value of care provided by this intervention. Health care policies to implement efficient prehospital triage and to accelerate in-hospital workflow are urgently needed.

High-frequency 10 kHz Spinal Cord Stimulation for Chronic Back and Leg Pain: Cost-consequence and Cost-effectiveness Analyses.

OBJECTIVES: There is good evidence that spinal cord stimulation (SCS) is effective for reducing chronic back and leg pain (CBLP). SENZA randomized controlled trial showed high-frequency (10 kHz) stimulation (10 kHz-SCS) is clinically superior to traditional low-frequency SCS (LF-SCS).Undertake cost-consequence and cost-effectiveness analysis of 10 kHz-SCS compared with LF-SCS. METHODS: A probabilistic decision tree and Markov decision analytic model was used to synthesize data on CBLP outcomes and costs over a 15-year time horizon from a UK National Health Service perspective using data from the SENZA randomized controlled trial and other publications. Results are expressed as incremental cost per quality-adjusted life year (QALY) in 2016 Pounds Sterling. RESULTS: 10 kHz-SCS is cost-saving and cost-effective compared with LF-SCS, with mean cost-savings of £7170 (95% confidence interval: £6767-£7573) and £3552 (95% confidence interval: £3313-£3792) per patient compared with nonrechargeable and rechargeable LF-SCS devices, respectively. 10 kHz-SCS has a 95% likelihood of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY. Our findings were robust across a wide range of sensitivity analyses. CONCLUSIONS: There is a strong economic case for choosing 10 kHz-SCS over LF-SCS for CBLP. Furthermore, 10 kHz-SCS has clinical advantages not captured in our analysis, including shorter, and more predictable procedure times.

Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke.

Background and Purpose- The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods- A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy-treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results- Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy-treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively. Conclusions- Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

Steroids and miRNAs in assessment of ovarian tissue damage following cryopreservation.

Ovarian cortical tissue cryopreservation is a relatively novel approach to preserving fertility in women diagnosed with cancer. However, the effects of freezing-thawing are not fully understood, mainly due to the lack of suitable methods to assess tissue's survival after thawing. Disparities in steroid production have been associated with ovarian failure by disrupting folliculogenesis, ovulation and oocyte apoptosis. Moreover, specific microRNAs, identified in human ovarian follicles, are thought to play a fundamental role in folliculogenesis. In this study, we investigated the possible interplay between the ovarian steroidal production and microRNA expression patterns in spent culture media, as potential non-invasive markers for ovarian tissue damage after cryopreservation. Cryopreservation of ovarian cortical tissue decreased (P<0.05) both steroid production (oestradiol and progesterone) and expression of microRNA-193b and 320A in spent culture media over 5 days, however, expression of microRNA-24 increased (P<0.05). The number of primordial follicles were also reduced (P<0.05) in fresh-cultured and cryopreserved-cultured cortical tissues when compared with fresh tissues. Downregulation of microRNA-193b and microRNA-320A together with upregulation of microRNA-24 could have a synergistic role in cell apoptosis, and consequently leading to reduced oestradiol and progesterone production. Thus, there appears to be an interplay between these microRNAs, ovarian steroid production and cell damage, which can be further explored as novel non-invasive markers of cell damage following cryopreservation.