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.

Collateral Capacity Assessment : Robustness and Interobserver Agreement of Two Grading Scales and Agreement with Quantitative Scoring.

BACKGROUND AND PURPOSE: Intracranial collateral capacity is conducive to imply parenchymal perfusion of affected territory after acute vessel occlusion. The Tan collateral score is commonly used to assess the intracranial collateral capacity; however, this score is coarsely grained and interobserver agreement is low, which reduces prognostic value and clinical utility. We introduce and evaluate an alternative extended Tan score based on the conventional Tan scale and assess the agreement with a quantitative score. METHODS: We included 100 consecutive patients with a proven acute single large vessel occlusion of the proximal anterior circulation. Collaterals were graded with the conventional and extended Tan score and an automated quantitative score. The extended Tan score is a finer 6­scale manual score based on the conventional 4­point Tan scale. The quantitative score is calculated by an automatic software package (StrokeViewer). Interobserver agreement of the manual scores was assessed with the weighted kappa. The Spearman correlation coefficient was calculated to determine the agreement between the manual and automated collateral scores. RESULTS: The interobserver agreement was higher for the extended score than for the conventional score with a weighted kappa of 0.70 and 0.65, respectively. For the extended and conventional score, the Spearman correlation coefficient for the agreement with the automated score was 0.78 and 0.76, respectively. CONCLUSION: Because of the good interobserver agreement and good agreement with quantitative assessment, the extended collateral score is a strong candidate to improve prognostic value of collateral assessment and implementation in clinical practice.

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.

Health economic impact of first-pass success among patients with acute ischemic stroke treated with mechanical thrombectomy: a United States and European perspective.

BACKGROUND: First-pass effect (FPE), restoring complete or near complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) in a single pass, is an independent predictor for good functional outcomes in the endovascular treatment of acute ischemic stroke. The economic implications of achieving FPE have not been assessed. OBJECTIVE: To assess the economic impact of achieving complete or near complete reperfusion after the first pass. METHODS: Post hoc analyses were conducted using ARISE II study data. The target population consisted of patients in whom mTICI 2c-3 was achieved, stratified into two groups: (1) mTICI 2c-3 achieved after the first pass (FPE group) or (2) after multiple passes (non-FPE group). Baseline characteristics, clinical outcomes, and healthcare resource use were compared between groups. Costs from peer-reviewed literature were applied to assess cost consequences from the perspectives of the United States (USA), France, Germany, Italy, Spain, Sweden, and United Kingdom (UK). RESULTS: Among patients who achieved mTICI 2c-3 (n=172), FPE was achieved in 53% (n=91). A higher proportion of patients in the FPE group reached good functional outcomes (90-day modified Rankin Scale score 0-2 80.46% vs 61.04%, p<0.01). The patients in the FPE group had a shorter mean length of stay (6.10 vs 9.48 days, p<0.01) and required only a single stent retriever, whereas 35% of patients in the non-FPE group required at least one additional device. Driven by improvement in clinical outcomes, the FPE group had lower procedural/hospitalization-related (24-33% reduction) and annual care (11-27% reduction) costs across all countries. CONCLUSIONS: FPE resulted in improved clinical outcomes, translating into lower healthcare resource use and lower estimated costs.

qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients.

BACKGROUND: The Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading. AIMS: We present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology. METHODS: We included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0-2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors. RESULTS: In total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58-88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome. CONCLUSION: qTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score.

Utility-Weighted Modified Rankin Scale as Primary Outcome in Stroke Trials: A Simulation Study.

BACKGROUND AND PURPOSE: The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a new patient-centered primary outcome in stroke trials. We aimed to describe utility weights for the mRS health states and to evaluate the statistical efficiency of the UW-mRS to detect treatment effects in stroke intervention trials. METHODS: We used data of the 500 patients enrolled in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Utility values were elicited from the EuroQol Group 5-Dimension Self-Report Questionnaire assessed at 90 days after inclusion, simultaneously with the mRS. Utility weights were determined by averaging the utilities of all patients within each mRS category. We performed simulations to evaluate statistical efficiency. The simulated treatment effect was an odds ratio of 1.65 in favor of the treatment arm, similar for all mRS cutoffs. This treatment effect was analyzed using 3 approaches: linear regression with the UW-mRS as outcome, binary logistic regression with a dichotomized mRS (0-1/2-6, 0-2/3-6, and 0-4/5-6), and proportional odds logistic regression with the ordinal mRS. The statistical power of the 3 approaches was expressed as the proportion of 10 000 simulations that resulted in a statistically significant treatment effect (P≤0.05). RESULTS: The mean utility values (SD) for mRS categories 0 to 6 were: 0.95 (0.08), 0.93 (0.13), 0.83 (0.21), 0.62 (0.27), 0.42 (0.28), 0.11 (0.28), and 0 (0), respectively, but varied substantially between individual patients within each category. The UW-mRS approach was more efficient than the dichotomous approach (power 85% versus 71%) but less efficient than the ordinal approach (power 85% versus 87%). CONCLUSIONS: The UW-mRS as primary outcome does not capture individual variation in utility values and may reduce the statistical power of a randomized trial.

Stroke treatment academic industry roundtable: research priorities in the assessment of neurothrombectomy devices.

BACKGROUND AND PURPOSE: The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke. SUMMARY OF REVIEW: Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue. CONCLUSIONS: Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

Vertebral augmentation: update on safety, efficacy, cost effectiveness and increased survival?

Although over 300 articles have been published annually on vertebral augmentation in the last 5 years, there remains much debate about a fundamental question - is vertebral augmentation a safe and effective treatment to achieve analgesia, reduce disability, and improve quality of life in patients with a vertebral fracture? In this modern era of evidence-based clinical practice and public health care policy and funding, an evidentiary basis is needed to continue to perform vertebral augmentation. The aim of this narrative review is to summarize the latest and highest quality evidence for efficacy, safety, cost effectiveness, and potential survival benefit after vertebroplasty and kyphoplasty. The design, major inclusion criteria, primary outcome measures, relevant primary baseline characteristics, primary outcomes, relevant secondary outcomes, and limitations of prospective multicenter randomized sham-controlled and conservative management-controlled trials are summarized. Recently published meta-analyses or systematic reviews of efficacy that include these recent prospective studies of vertebral augmentation are examined. The highest quality procedural safety data relating to medical complications, cement leaks, and subsequent vertebral fracture are reviewed. Publications from national databases analyzing potential reduction in length of hospital stay and reduction in mortality after vertebral augmentation are presented. Finally, emerging literature assessing the potential cost-effectiveness of vertebral augmentation is considered. This narrative review will provide interventional pain physicians a summary of the latest and highest quality data published on vertebral augmentation. This will allow integration of the best available evidence with clinical expertise and patient wishes to make the most appropriate evidence-based clinical decisions for patients with symptomatic vertebral fracture.

The use of advanced imaging and representation of workers compensation in vertebral augmentation: a single-center comparison with the INVEST Trial.

BACKGROUND: Vertebral augmentation (VA) techniques have changed the paradigm of treatment during the past decade and involve injection of polymethylmethacrylate (PMMA) cement directly into a compressed vertebral body. During the summer of 2009, the INVEST trial was one of 2 randomized controlled studies that reported equivalence between vertebroplasty and a control procedure.  OBJECTIVE: In this analysis, we sought to compare the subset of patients studied in the INVEST trial to a tertiary academic institution with respect to 2 variables: Workers compensation status and presence of advanced imaging prior to the procedure. STUDY DESIGN: Retrospective review of 634 procedures. METHODS: We performed a retrospective review of 634 vertebral augmentation procedures at our institution between June 2004 and August 2008, overlapping with the dataset of the INVEST trial. The primary comparison was whether patients received Workers compensation and/or advanced imaging prior to the procedure. The study was IRB approved, and in accordance with HIPAA guidelines. RESULTS: There were 409 patients who underwent 634 procedures between June 2004 and August 2008. Among 634 procedures, only 3 included Workers compensation. Therefore, the majority of patients (> 99%) did not receive Workers compensation compared to the INVEST trial (11 - 13%). Similarly, in 629 out of 634 procedures (99.2%), patients underwent advanced imaging comprised of magnetic resonance imaging (MRI), computed tomography (CT) or bone scan. LIMITATIONS: We simply looked at 2 elements of the patient demographic in a time-matched fashion and compared it to the U.S. based INVEST trial. It is possible that despite our diligent efforts to review the data set, we have inadvertently excluded some patients, the incorporation of whom might have changed the statistics. CONCLUSION: We reviewed our time-matched database in terms of 2 variables we thought curious in the INVEST trial.  In comparison to our practice, where advanced imaging is essentially required and Workers compensation largely not seen, these aspects of the INVEST trial's population stood out.

Effects of a music intervention on patients undergoing cerebral angiography: a pilot study.

PURPOSE: To test the effect of a music intervention on procedural anxiety, stress response and medication requirements in participants with a cerebral aneurysm or arteriovenous malformation (AVM) undergoing cerebral angiography. METHOD AND MATERIALS: A prospective pilot study was conducted using an experimental two group pre-test, post-test design. 48 participants were randomly assigned to a control group (standard care) or experimental group (standard care plus self-selected music via overhead stereo system). The stress response was measured by heart rate (HR) and systolic blood pressure (SBP) at baseline, and during and following the procedure. Anxiety was measured by the State Trait Anxiety Inventory for Adults (STAI) before and after the procedure, and total medications administered periprocedurally were recorded. RESULTS: 24 participants in each group were enrolled. R-ANCOVA revealed non-significant findings for HR (F=1.4; p=0.27; power=0.38) and SBP (F=2.1; p=0.10; power=0.57). The ANCOVA for anxiety revealed significantly lower STAI scores in the control group (F=3.8; p=0.003) compared with the experimental group. Independent t test analysis for the total doses of fentanyl and midazolam were found to be F=0.08, p=0.78 and F=0.38, p=0.54, respectively. CONCLUSION: A music intervention on participants with a brain aneurysm or AVM undergoing cerebral angiography did not have a statistically significant impact on reducing the stress response, anxiety or medication requirements. Interestingly, participants in the control group had significantly less anxiety after their angiogram than did participants in the experimental group. This pilot study sets the stage for future research to further examine these findings.