Rates and reasons for hospital readmission after acute ischemic stroke in a US population-based cohort.

Hospital readmissions following stroke are costly and lead to worsened patient outcomes. We examined readmissions rates, diagnoses at readmission, and risk factors associated with readmission following acute ischemic stroke (AIS) in a large United States (US) administrative database. Using the 2019 Nationwide Readmissions Database, we identified adults discharged with AIS (ICD-10-CM I63*) as the principal diagnosis. Survival analysis with Weibull accelerated failure time regression was used to examine variables associated with hospital readmission. In 2019, 273,811 of 285,451 AIS patients survived their initial hospitalization. Of these, 60,831 (22.2%) were readmitted within 2019. Based on Kaplan Meyer analysis, readmission rates were 9.7% within 30 days and 30.5% at 1 year following initial discharge. The most common causes of readmissions were stroke and post stroke sequalae (25.4% of 30-day readmissions, 15.0% of readmissions between 30-364 days), followed by sepsis (10.3% of 30-day readmissions, 9.4% of readmissions between 30-364 days), and acute renal failure (3.2% of 30-day readmissions, 3.0% of readmissions between 30-364 days). After adjusting for multiple patient and hospital-level characteristics, patients at increased risk of readmission were older (71.6 vs. 69.8 years, p<0.001) and had longer initial lengths of stay (7.6 vs. 6.2 day, p<0.001). They more often had modifiable comorbidities, including vascular risk factors (hypertension, diabetes, atrial fibrillation), depression, epilepsy, and drug abuse. Social determinants associated with increased readmission included living in an urban (vs. rural) setting, living in zip-codes with the lowest median income, and having Medicare insurance. All factors were significant at p<0.001. Unplanned hospital readmissions following AIS were high, with the most common reasons for readmission being recurrent stroke and post stroke sequalae, followed by sepsis and acute renal failure. These findings suggest that efforts to reduce readmissions should focus on optimizing secondary stroke and infection prevention, particularly among older socially disadvantaged patients.

Cost-Effectiveness of Cilostazol Added to Aspirin or Clopidogrel for Secondary Prevention After Noncardioembolic Stroke.

Background The objective of the study was to assess the cost-effectiveness of cilostazol (a selective phosphodiesterase 3 inhibitor) added to aspirin or clopidogrel for secondary stroke prevention in patients with noncardioembolic stroke. Methods and Results A Markov model decision tree was used to examine lifetime costs and quality-adjusted life years (QALYs) of patients with noncardioembolic stroke treated with either aspirin or clopidogrel or with additional cilostazol 100 mg twice daily. Cohorts were followed until all patients died from competing risks or ischemic or hemorrhagic stroke. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model 10 000 cohorts of 10 000 patients. The addition of cilostazol to aspirin or clopidogrel is strongly cost saving. In all 10 000 simulations, the cilostazol strategy resulted in lower health care costs compared with aspirin or clopidogrel alone (mean $13 488 cost savings per patient; SD, $8087) and resulted in higher QALYs (mean, 0.585 more QALYs per patient lifetime; SD, 0.290). This result remained robust across a variety of sensitivity analyses, varying cost inputs, and treatment effects. At a willingness-to-pay threshold of $50 000/QALY, average net monetary benefit from the addition of cilostazol was $42 743 per patient over their lifetime. Conclusions Based on the best available data, the addition of cilostazol to aspirin or clopidogrel for secondary prevention following noncardioembolic stroke results in significantly reduced health care costs and a gain in lifetime QALYs.

Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hours After Symptom Onset: A Pooled Analysis of the AURORA Database.

Importance: The optimal imaging approach for identifying patients who may benefit from endovascular thrombectomy (EVT) beyond 6 hours after they were last known well is unclear. Six randomized clinical trials (RCTs) have evaluated the efficacy of EVT vs standard medical care among patients with ischemic stroke. Objective: To assess the benefits of EVT among patients with 3 baseline imaging profiles using a pooled analysis of RCTs. Data Sources: The AURORA (Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well) Collaboration pooled patient-level data from the included clinical trials. Study Selection: An online database search identified RCTs of endovascular stroke therapy published between January 1, 2010, and March 1, 2021, that recruited patients with ischemic stroke who were randomized between 6 and 24 hours after they were last known well. Data Extraction/Synthesis: Data from the final locked database of each study were provided. Data were pooled, and analyses were performed using mixed-effects modeling with fixed effects for parameters of interest. Main Outcomes and Measures: The primary outcome was reduction in disability measured by the modified Rankin Scale at 90 days. An evaluation was also performed to examine whether the therapeutic response differed based on imaging profile among patients who received treatment based on the time they were last known well. Treatment benefits were assessed among a clinical mismatch subgroup, a target perfusion mismatch subgroup, and an undetermined profile subgroup. The primary end point was assessed among these subgroups and during 3 treatment intervals (tercile 1, 360-574 minutes [6.0-9.5 hours]; tercile 2, 575-762 minutes [9.6-12.7 hours]; and tercile 3, 763-1440 minutes [12.8-24.0 hours]). Results: Among 505 eligible patients, 266 (mean [SD] age, 68.4 [13.8] years; 146 women [54.9%]) were assigned to the EVT group and 239 (mean [SD] age, 68.7 [13.7] years; 126 men [52.7%]) were assigned to the control group. Among 295 patients in the clinical mismatch subgroup and 359 patients in the target perfusion mismatch subgroup, EVT was associated with reductions in disability at 90 days vs no EVT (clinical mismatch subgroup, odds ratio [OR], 3.57; 95% CI, 2.29-5.57; P < .001; target perfusion mismatch subgroup, OR, 3.13; 95% CI, 2.10-4.66; P = .001). Statistically significant benefits were observed in all 3 terciles for both subgroups, with the highest OR observed for tercile 3 (clinical mismatch subgroup, OR, 4.95; 95% CI, 2.20-11.16; P < .001; target perfusion mismatch subgroup, OR, 5.01; 95% CI, 2.37-10.60; P < .001). A total of 132 patients (26.1%) had an undetermined imaging profile and no significant treatment benefit (OR, 1.59; 95% CI, 0.82-3.06; P = .17). The interaction between treatment effects for the clinical and target perfusion mismatch subgroups vs the undetermined profile subgroup was significant (OR, 2.28; 95% CI, 1.11-4.70; P = .03). Conclusions and Relevance: In this study, EVT was associated with similar benefit among patients in the clinical mismatch and target perfusion mismatch subgroups during the 6- to 24-hour treatment interval. These findings support EVT as a treatment for patients meeting the criteria for either of the imaging mismatch profiles within the 6- to 24-hour interval.

A dynamic simulation framework for CT perfusion in stroke assessment built from first principles.

PURPOSE: Physicians utilize cerebral perfusion maps (e.g., cerebral blood flow, cerebral blood volume, transit time) to prescribe the plan of care for stroke patients. Variability in scanning techniques and post-processing software can result in differences between these perfusion maps. To determine which techniques are acceptable for clinical care, it is important to validate the accuracy and reproducibility of the perfusion maps. Validation using clinical data is challenging due to the lack of a gold standard to assess cerebral perfusion and the impracticality of scanning patients multiple times with different scanning techniques. In contrast, simulated data from a realistic digital phantom of the cerebral perfusion in acute stroke patients would enable studies to optimize and validate the scanning and post-processing techniques. METHODS: We describe a complete framework to simulate CT perfusion studies for stroke assessment. We begin by expanding the XCAT brain phantom to enable spatially varying contrast agent dynamics and incorporate a realistic model of the dynamics in the cerebral vasculature derived from first principles. A dynamic CT simulator utilizes the time-concentration curves to define the contrast agent concentration in the object at each time point and generates CT perfusion images compatible with commercially available post-processing software. We also generate ground truth perfusion maps to which the maps generated by post-processing software can be compared. RESULTS: We demonstrate a dynamic CT perfusion study of a simulated patient with an ischemic stroke and the resulting perfusion maps generated by post-processing software. We include a visual comparison between the computer-generated perfusion maps and the ground truth perfusion maps. The framework is highly tunable; users can modify the perfusion properties (e.g., occlusion location, CBF, CBV, and MTT), scanner specifications (e.g., focal spot size and detector configuration), scanning protocol (e.g., kVp and mAs), and reconstruction parameters (e.g., slice thickness and reconstruction filter). CONCLUSIONS: This framework provides realistic test data with the underlying ground truth that enables a robust assessment of CT perfusion techniques and post-processing methods for stroke assessment.

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study.

BACKGROUND: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. METHODS: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials. RESULTS: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. CONCLUSIONS: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02446587.

Effect of Sex on Clinical Outcome and Imaging after Endovascular Treatment of Large-Vessel Ischemic Stroke.

BACKGROUND AND PURPOSE: It is unclear if sex differences explain some of the variability in the outcomes of stroke patients who undergo endovascular treatment (EVT). In this study we assess the effect of sex on radiological and functional outcomes in EVT-treated acute stroke patients and determine if differences in baseline perfusion status between men and women might account for differences in outcomes. METHODS: We included patients from the CRISP (Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke) study, a prospective cohort study of acute stroke patients who underwent EVT up to 18 hours after last seen well. We designed ordinal regression and univariable and multivariable regression models to examine the association between sex and infarct growth, final infarct volume and 90-day mRS score. RESULTS: We included 198 patients. At baseline, women had smaller perfusion lesions, more often had a target mismatch perfusion profile, and had better collateral perfusion. Women experienced less ischemic core growth (median 15 mL vs. 29 mL, p < 0.01) and had smaller final infarct volumes (median 26 mL vs. 50 mL, p < 0.01). Female sex was associated with a favorable shift on the modified Rankin Scale (adjusted cOR 1.79 [1.04 - 3.08; p = 0.04]) and lower odds of severe disability or death (adjusted OR 0.29 [0.10 - 0.81]; p = 0.02). CONCLUSIONS: The results suggest that women have better collaterals and, therefore, more often exhibit a favorable imaging profile on baseline imaging, experience less lesion growth, and have better clinical outcomes following endovascular therapy.

Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes.

BACKGROUND AND PURPOSE: The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature. METHODS: We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time. RESULTS: We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T0 plus 1.6 times the width of the venous output function (P<0.001; R2=0.49). CONCLUSIONS: This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended.

Cost comparison between the atraumatic and cutting lumbar puncture needles.

OBJECTIVE: The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache. METHODS: A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model. RESULTS: Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year. CONCLUSION: The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.

Cost-effectiveness of tissue-type plasminogen activator in the 3- to 4.5-hour time window for acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to determine the cost-effectiveness of tissue-type plasminogen activator (tPA) treatment in the 3- to 4.5-hour time window after ischemic stroke. METHODS: Decision-analytic and Markov state-transition models were created to determine the cost-effectiveness of treatment of ischemic stroke patients with intravenous tPA administered in the 3- to 4.5-hour time window compared with medical therapy without tPA. Health benefits were measured in quality-adjusted life-years (QALYs). The economic outcome measure of the model was the difference in estimated healthcare costs between the 2 treatment alternatives. The incremental cost-effectiveness ratio was calculated by dividing the cost difference by the difference in QALYs. One-way sensitivity and probabilistic analyses were performed to test the robustness of the model. RESULTS: The administration of tPA compared with standard medical therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of $6050, yielding an incremental cost-effectiveness ratio of $21 978 per QALY. One-way sensitivity analyses demonstrated that the incremental cost-effectiveness ratio was most sensitive to the cost of hospitalization for patients who received tPA. Based on probabilistic analysis, there is an 88% probability that tPA is the preferred treatment at a willingness-to-pay threshold of $50 000 per QALY. CONCLUSIONS: The balance of costs and benefits favors treatment with intravenous tPA in the 3- to 4.5-hour time window. This supports, from a societal perspective, the use of tPA therapy in this treatment time window for acute ischemic stroke.

Two aces: transient ischemic attack work-up as outpatient assessment of clinical evaluation and safety.

BACKGROUND AND PURPOSE: To evaluate a novel emergency department-based TIA triage system. METHODS: We developed an approach to TIA triage and management based on risk assessment using the ABCD(2) score in combination with early cervical and intracranial vessel imaging. It was anticipated that this triage system would avoid hospitalization for the majority of TIA patients and result in a low rate of recurrent stroke. We hypothesized that the subsequent stroke rate among consecutively encountered patients managed with this approach would be lower than predicted based on their ABCD2 scores. RESULTS: From June 2007 to December 2009, 224 consecutive patients evaluated in the Stanford emergency department for a possible TIA were enrolled in the study. One hundred fifty-seven were discharged to complete their evaluation at the outpatient TIA clinic; 67 patients were hospitalized. One hundred sixteen patients had a final diagnosis of TIA/minor stroke or possible TIA. The stroke rates at 7, 30, and 90 days were 0.6% (0.1%-3.5%) for patients referred to the TIA clinic and 1.5% (0.3%-8.0%) for the hospitalized patients. Combining both groups, the overall stroke rate was 0.9% (0.3%-3.2%), which is significantly less than expected based on ABCD2 scores (P=0.034 at 7 days and P=0.001 at 90 days). CONCLUSIONS: This emergency department-based inpatient versus outpatient TIA triage system led to a low rate of hospitalization (30%). Recurrent stroke rates were low for both the hospitalized and outpatient subgroups.

Cost-effectiveness analysis of mechanical thrombectomy in acute ischemic stroke.

OBJECT: Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window. In this study, the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with standard medical therapy in patients who are ineligible to receive tissue plasminogen activator. METHODS: Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate (18 vs 60%) and a lower rate of symptomatic intracranial hemorrhage (0.6 vs 7.8%) than the active treatment group. A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with standard medical therapy. All probabilities, quality-of-life factors, and costs were estimated from the published literature. Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes. RESULTS: Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality-adjusted life years (QALYs), compared with standard medical therapy (2.37 vs 1.83 QALYs), at an increased cost of $6600. This yielded an incremental cost-effectiveness ratio (ICER) of $12,120 per QALY gained, a value generally considered cost-effective. Sensitivity analysis showed that mechanical thrombectomy remained cost-effective (ICER < $50,000 per QALY gained) for all model inputs varied over a reasonable range, except for age at stroke treatment. For patients older than 82 years of age, the treatment was only borderline cost-effective (ICER of $50,000-100,000 per QALY gained). CONCLUSIONS: The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be costeffective. These results require validation when data from a randomized, controlled trial of mechanical thrombectomy become available.