Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

BACKGROUND: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. METHODS: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. RESULTS: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. CONCLUSIONS: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.

Nationwide Incidence and Trends in Central Retinal Arterial Occlusion Management: A 5000-Patient Analysis.

Central retinal artery occlusion (CRAO) is a rare and visually debilitating vascular condition characterized by sudden and severe vision loss. CRAO is a compelling target for intravenous alteplase (tPA) and endovascular mechanical thrombectomy (MT) due to pathophysiological similarities with acute ischemic stroke; however, the utility of these interventions in CRAO remains dubious due to limited sample sizes and potential risks. To assess usage and outcomes of tPA and MT in CRAO, we queried the National Inpatient Sample database using International Classification of Disease, Ninth and Tenth edition for patients with CRAO and acute ischemic stroke between 2010 and 2019. Our cohort of 5009 CRAO patients were younger with higher rates of obesity, hypertension, long-term anticoagulant use, and tobacco use compared to acute ischemic stroke patients. CRAO patients had lower rates of tPA administration (3.41% vs 6.21%) and endovascular MT (0.38% vs 1.31%) but fewer complications, including deep vein thrombosis, pneumonia, urinary tract infection, acute kidney injury, and acute myocardial infarction (all P < 0.01). CRAO patients had lower rates of poor functional outcome (31.74% vs 58.1%) and in-hospital mortality (1.2% vs 5.64%), but higher rates of profound blindness (9.24% vs 0.58%). A multivariate regression showed no relationship between tPA and MT and profound blindness, although the limited sample size of patients receiving interventions may have contributed to this apparent insignificance. Further investigation of larger patient cohorts and alternative treatment modalities could provide valuable insights for revascularization therapies in CRAO to optimize visual restoration and clinical outcomes.

Economic evaluation of intravenous alteplase for stroke with the time of onset between 4.5 and 9 hours.

BACKGROUND: A clinical trial proved the clinical effectiveness of perfusion imaging-guided intravenous thrombolysis with alteplase for patients with acute ischemic stroke (AIS) with the time of onset between 4.5 and 9 hours. This study aimed to assess the lifetime cost-effectiveness of alteplase versus placebo from the perspective of Chinese and United States (US) healthcare payers. METHODS: A decision-analytic model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) associated with alteplase or placebo. Model inputs were extracted from published sources. Incremental costs, incremental QALYs, and incremental cost-effectiveness ratio (ICER) were calculated to evaluate the base-case scenario. One-way and probabilistic sensitivity analysis were performed to evaluate uncertainty in the results. RESULTS: In China, alteplase yielded an additional lifetime QALY of 0.126 with an additional cost of Chinese Yuan (¥) ¥9552 compared with placebo, and the ICER was ¥83 950 (US$12 157)/QALY. In the US, alteplase had a higher QALY (difference: 0.193) with a lower cost (difference: US$-2024) compared with placebo. In probabilistic sensitivity analyses, alteplase had a 42.54% to 78.3% probability of being cost-effective compared with placebo in China when the willingness-to-pay (WTP) threshold ranged from ¥72 447/QALY to ¥217 341/QALY. In the US, alteplase had a 93.47% to 93.57% probability of being cost-effective under the WTP threshold of US$100 000/QALY to US$150 000/QALY. These findings remained robust under one-way sensitivity analysis. CONCLUSION: For patients with AIS with a time of onset between 4.5 and 9 hours, perfusion imaging-guided intravenous alteplase was likely to be cost-effective in China and was cost-effective in the US when compared with placebo.

Assessment of histological characteristics, imaging markers, and rt-PA susceptibility of ex vivo venous thrombi.

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ, which prohibits mechanistic investigation of lytic resistance or the development of diagnostic indicators for treatment outcomes. In this study, thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. A wide range of thrombus morphologies were observed, with a dependence on age and etymology of the specimen. Fibrinolytic inhibitors including PAI-1, alpha 2-antiplasmin, and TAFI were present in samples, which may contribute to the response venous thrombi to catheter-directed thrombolytics. Finally, a weak but significant correlation was observed between the response of the sample to lytic drug and its magnetic microstructure assessed with a quantitative MRI sequence. These findings highlight the myriad of changes in venous thrombi that may promote lytic resistance, and imaging metrics that correlate with treatment outcomes.

Fast-track thrombolysis protocol for acute limb ischemia.

OBJECTIVE: Catheter-directed thrombolysis in the treatment of acute lower extremity arterial occlusions often requires several interventional sessions to generate successful outcomes. It is typically an expensive procedure, necessitating extended hospital length of stay (LOS) that may be associated with an increase in both local and systemic hemorrhagic complications. Five years ago, we created the fast-track thrombolysis protocol for arteries (FTTP-A) to deal with these concerns. The goal of our protocol is to re-establish patency during the first session of thrombolysis, thus decreasing costs and complications associated with prolonged periods of thrombolytic exposure. METHODS: A retrospective study of 42 patients who were treated for acute limb ischemia at our institution by FTTP-A from January 2014 to February 2019 was performed. FTTP-A includes periadventitial lidocaine injection at the arterial puncture site under ultrasound guidance, contrast arteriography of the entire targeted segment, pharmacomechanical rheolytic thrombectomy of the occluded arterial segment, tissue plasminogen activator infusion along the occluded segment, balloon maceration of the thrombus, and (if deemed necessary) placement of a stent in an area of significant (≥30%) stenosis that is refractory to balloon angioplasty and thrombolysis. After the stenosis or thrombus is cleared, patients are prescribed an oral anticoagulant agent. RESULTS: Primary FTTP-A (50 total interventions) was performed in 42 patients. The median age of patients was 67.2 ± 12.2 years (range, 41-98 years), and 54.8% were male; 59.5% of the procedures were performed on the left lower extremity. Initial arterial access was obtained through the common femoral artery in 39 of 42 cases (92.9%); in the remaining 3 cases, it was obtained in a left bypass access site, a right femoral-popliteal graft, and a right femoral-femoral graft. The mean operative time was 148.9 ± 62.9 minutes (range, 83-313 minutes), and the mean volume of tissue plasminogen activator infused was 9.7 ± 4.0 mg (range, 2-20 mg). The median cost including medications and interventional tools was $4673.19 per procedure. The mean postoperative LOS was 3.1 ± 4.5 days (range, 1-25 days). Median postoperative LOS was 1 day. Mean postoperative follow-up was 27 ± 19.2 months (range, 0-62 months). Single-session FTTP-A was successful in 81% (n = 34/42) of patients; the remaining 8 patients (19%) required a single additional session. Of the 42 patients, 34 (81%) required arterial stenting. Periprocedural complications consisted of one patient with hematuria, which resolved, and one patient with thrombocytopenia, which resolved. No patients experienced rethrombosis within 30 days of FTTP-A. During the 5-year study period, there was no significant local or systemic hemorrhage, limb loss, or mortality related to this protocol. CONCLUSIONS: FTTP-A appears to be a safe, efficacious, and cost-effective procedure in the resolution of acute lower extremity arterial occlusions.

Assessment of eligibility for thrombolysis in acute ischaemic stroke patients in Morocco.

INTRODUCTION: intravenous thrombolysis with recombinant tissue plasminogen activator (rTPA) is an approved treatment for acute ischaemic stroke (AIS). However, its use remains low. We aimed to assess the eligibility of thrombolysis for our patients with AIS before implementing this treatment method in our teaching hospital. METHODS: we conducted a prospective cross-sectional study in the emergency department of Casablanca University Hospital. We included every patient admitted for a stroke-related symptom. Delays between symptom-onset and admission and delays regarding the in-hospital evaluation of patients were recorded. Patients eligible for intravenous thrombolytic therapy were identified according to American Heart Association guidelines. RESULTS: in all, 463 patients were included. Only 8.42% of patients were eligible for thrombolysis; 74% of patients were ineligible because of an onset-to-thrombolysis delay longer than 4.5 hours. Mean onset-to-thrombolysis time was 27.2 hours. Patients were admitted with a mean delay of 24.9 hours. The in-hospital evaluation, from admission to computerized tomography (CT) interpretation, averaged 2.3 hours in length. CONCLUSION: the percentage of patients eligible for thrombolysis remains very low in our structure. The majority would not have benefitted from the therapy because of an extra hospital delay far exceeding the recommended therapeutic window. To shorten our delays and increase the number of patients benefiting from thrombolysis, we must implement strategies aiming to improve the recognition, evaluation and management of patients from the general public to the neurovascular unit.

Sex and racial disparity in utilization and outcomes of t-PA and thrombectomy in acute ischemic stroke.

BACKGROUND/PURPOSE: Racial/ethnic and sex disparity may occur in stroke throughout the continuum of care. Endovascular therapy (EVT) became standard of care in 2015 for eligible patients with acute ischemic stroke (AIS). We evaluated for racial and sex differences in t-PA and EVT utilization and outcomes in 2016 in the National Inpatient Sample. METHODS: Treatment rates for t-PA, EVT, and t-PA+EVT and outcomes including home discharge, in-hospital mortality and prolonged length of stay (pLOS) were evaluated by sex and race. Multivariate survey-logistic regression was performed to evaluate outcomes. RESULTS: The study had 468,630 patients - 49.3% men, 50.7% women; 69.3% whites, and 30.7% non-whites. There was no difference in treatment utilization by sex, women vs men for t-PA (7.65% vs 7.76%; aOR:1.02; 95% CI:0.97-1.07), EVT (1.74% vs 1.67%; aOR:1.09; 95% CI:0.99-1.20) and t-PA+EVT (0.57% vs 0.57%; aOR:1.01; 95% CI:0.85-1.21); and by race, non-white vs white for t-PA (7.62% vs 7.74%; aOR:0.98; 95% CI:0.93-1.05), EVT (1.62% vs 1.74%; aOR:0.91; 95% CI:0.78-1.07), and t-PA+EVT(0.59% vs 0.56%; aOR:1.05; 95% CI:0.84-1.30). Compared to men, women treated with t-PA had less home discharge (37.2% vs 46.3%; aOR:0.81; 95% CI:0.72-0.90), more in-hospital mortality (5.7% vs 3.9%; aOR:1.37; 95% CI:1.06-1.77) and less pLOS (8.3% vs 9.6%; aOR:0.82; 95% CI:0.69-0.98); women treated with EVT had less home discharge (15.8% vs 23.7%; aOR:0.69; 95% CI:0.52-0.91). Compared to whites, non-whites treated with t-PA had lower odds of home discharge (42.1% vs 41.6%; aOR:0.79; 95% CI:0.69-0.90), less in-hospital mortality (3.7% vs 5.3%; aOR:0.65; 95% CI:0.49-0.87), and higher pLOS (11.4% vs 7.9%; aOR:1.3; 95% CI:1.07-1.56); non-whites treated with EVT had less home discharge (18%vs 20.2%; aOR:0.70; 95% CI:0.51-0.97) and higher pLOS (35.1% vs 24%; aOR:1.52; 95% CI:1.16-1.99). CONCLUSION: Sex and racial disparity exists for outcomes of t-PA and EVT despite no difference in utilization rates.

Enhanced dispatch and rendezvous doubles the catchment area and number of patients treated on a mobile stroke unit.

INTRODUCTION: Mobile Stroke Units (MSUs) deliver acute stroke treatment on-scene in coordination with Emergency Medical Services (EMS). One criticism of the MSU approach is the limited range of a single MSU. The Houston MSU is evaluating MSU implementation, and we developed a rendezvous approach as an innovative solution to expand the range and number of patients treated. METHODS: In addition to direct 911 dispatch of our MSU to the scene within our 7-mile catchment area, we empowered more distant EMS units to activate the MSU. We also monitored EMS radio communications to identify possible patients. For these distant patients, the MSU met the EMS unit en route to the stroke center and treated the patient at that intermediate location. The distribution of the distance from MSU base station to site of stroke and time from 911 alert to tissue plasminogen activator (tPA) bolus were compared between patients treated on-scene and by rendezvous using Wilcoxon rank sum test. RESULTS: Over 4 years, 338 acute ischemic stroke patients were treated with tPA on our MSU. Of these, 169 (50%) were treated on-scene after MSU dispatch at a median of 6.4 miles (IQR 6.4 miles) from MSU base station. 169 (50%) were treated by 'rendezvous' pathway with assessment and treatment of stroke a median of 12.4 miles from base (IQR 5.5 miles) (p< 0.0001). Time (min) from MSU alert to tPA bolus did not differ: 36.0 ± 10.0 for on-scene vs 37.0 ± 10.0 with rendezvous (p=0.65). 13% of patients alerted via direct 911 dispatch were treated vs 44% of rendezvous patients. CONCLUSION: Adding a rendezvous approach to an MSU dispatch pathway doubles the range of operations and the number of patients treated by an MSU in an urban area, without incurring delay.

Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema: A Randomized Clinical Trial.

Importance: Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children. Objective: To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema. Design, Setting, and Participants: This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017. Interventions: Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation. Main Outcomes and Measures: The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost. Results: Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths. Conclusions and Relevance: The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema. Trial Registration: ClinicalTrials.gov identifier: NCT01717742.

Hospital Factors Associated With Interhospital Transfer Destination for Stroke in the Northeast United States.

Background We aimed to determine if there is an association between hospital quality and the likelihood of a given hospital being a preferred transfer destination for stroke patients. Methods and Results Data from Medicare claims identified acute ischemic stroke transferred between 394 northeast US hospitals from 2007 to 2011. Hospitals were categorized as transferring (n=136), retaining (n=241), or receiving (n=17) hospitals based on the proportion of acute ischemic stroke encounters transferred or received. We identified all 6409 potential dyads of sending and receiving hospitals, and categorized dyads as connected if ≥5 patients were transferred between the hospitals annually (n=82). We used logistic regression to identify hospital characteristics associated with establishing a connected dyad, exploring the effect of adjusting for different quality measures and outcomes. We also adjusted for driving distance between hospitals, receiving hospital stroke volume, and the number of hospitals in the receiving hospital referral region. The odds of establishing a transfer connection increased when rate of alteplase administration increased at the receiving hospital or decreased at the sending hospital, however this finding did not hold after applying a potential strategy to adjust for clustering. Receiving hospital performance on 90-day home time was not associated with likelihood of transfer connection. Conclusions Among northeast US hospitals, we found that differences in hospital quality, specifically higher levels of alteplase administration, may be associated with increased likelihood of being a transfer destination. Further research is needed to better understand acute ischemic stroke transfer patterns to optimize stroke transfer systems.

Safety and Outcomes of Intravenous tPA in Acute Ischemic Stroke Patients With Prior Stroke Within 3 Months: Findings From Get With The Guidelines-Stroke.

Background Guidelines recommend against the use of intravenous tPA (tissue-type plasminogen activator; IV tPA) in acute ischemic stroke patients with prior ischemic stroke within 3 months. However, there are limited data on the safety of IV tPA in this population. Methods and Results A retrospective observational study of patients ≥66 years of age linked to Medicare claims and treated with IV tPA at Get With The Guidelines-Stroke hospitals (February 2009 to December 2015). We identified 293 patients treated with IV tPA who had a prior ischemic stroke within 3 months and 30 655 with no history of stroke. Patients with prior stroke had a higher stroke severity (median National Institutes of Health Stroke Scale, 11 [6-19] versus 11 [6-18]; absolute standardized difference, 11.2%) and a higher prevalence of cardiovascular comorbidities. Patients with prior stroke had a higher unadjusted risk for symptomatic intracranial hemorrhage (7.7% versus 4.8%) and in-hospital mortality (12.6% versus 8.9%), but these differences were not statistically significant after adjustment. When stratified by prespecified time epochs, the elevated risk for symptomatic intracranial hemorrhage was seen only within the first 14 days (16.3% versus 4.8%; adjusted odds ratio [aOR], 3.7 [95% CI, 1.62-8.43]) but not in other epochs (2.1% versus 4.8%; aOR, 0.38 [95% CI, 0.05-2.79] for 15-30 days and 7.4% versus 4.8%; aOR, 1.36 [95% CI, 0.77-2.40] for 31-90 days). In addition, patients with prior stroke were significantly more likely to have a combined outcome of in-hospital mortality or discharge to hospice (25.9% versus 17.0%; aOR, 1.70 [95% CI, 1.21-2.38]), less likely to be discharged to home (28.3% versus 32.3%; aOR, 0.72 [95% CI, 0.54-0.98]), or to have good functional outcomes at discharge (modified Rankin Scale, 0-1; 11.3% versus 20.0%; aOR, 0.46 [95% CI, 0.24-0.89]). Conclusions Stroke providers need to continue to be vigilant about the safety of IV tPA in patients with prior stroke, particularly those with an event in the previous 14 days.

Redistributing medical resources for a bypass strategy for large vessel occlusion: a community-based study.

BACKGROUND: A bypass strategy for large vessel occlusion (LVO) benefits patients receiving endovascular thrombectomy (EVT), but may delay some patients from receiving IV thrombolysis. However, patient centralization has been shown to improve outcomes. OBJECTIVE: To understand the current coverage of medical services for patients with stroke, and to identify the best coverage under different medical resource redistribution to help balance medical equality and patient centralization. METHODS: This 6-year geographic study of 7679 on-scene patients with suspected stroke with a positive Cincinnati Prehospital Stroke Scale (CPSS) score identified 4037 patients with all three CPSS items who were suspected as having an LVO. Geographic, population, and patient coverage rates for hospitals providing IV thrombolysis and those providing EVT were identified according to hospital service areas, defined as geographic districts with access to a hospital within a ≤15 min off-peak driving time estimated using Google Maps. Moreover, we estimated the effects on resource redistribution when implementing a bypass strategy. RESULTS: Geographic coverage rates for hospitals providing IV thrombolysis and those providing EVT were 64.75% and 56.62%, respectively, and population coverage rates were 97.30% and 92.72%, respectively. The service areas of hospitals providing IV thrombolysis covered 93.77% of patients with suspected stroke, and those of hospitals providing EVT covered 87.89% of patients with suspected LVO. The number of hospitals providing IV thrombolysis and those providing EVT could be reduced to six and two hospitals, respectively, without affecting hospital arrival time when implementing a bypass strategy. CONCLUSION: Hospitals providing IV thrombolysis and EVT could be reduced without reducing medical equality.

Stroke Warning Information and Faster Treatment (SWIFT): Cost-Effectiveness of a Stroke Preparedness Intervention.

BACKGROUND: Less than 25% of stroke patients arrive to an emergency department within the 3-hour treatment window. OBJECTIVE: We evaluated the cost-effectiveness of a stroke preparedness behavioral intervention study (Stroke Warning Information and Faster Treatment [SWIFT]), a stroke intervention demonstrating capacity to decrease race-ethnic disparities in ED arrival times. METHODS: Using the literature and SWIFT outcomes for 2 interventions, enhanced educational (EE) materials, and interactive intervention (II), we assess the cost-effectiveness of SWIFT in 2 ways: (1) Markov model, and (2) cost-to-outcome ratio. The Markov model primary outcome was the cost per quality-adjusted life-year (QALY) gained using the cost-effectiveness threshold of $100 000/QALY. The primary cost-to-outcome endpoint was cost per additional patient with ED arrival <3 hours, stroke knowledge, and preparedness capacity. We assessed the ICER of II and EE versus standard care (SC) from a health sector and societal perspective using 2015 USD, a time horizon of 5 years, and a discount rate of 3%. RESULTS: The cost-effectiveness of the II and EE programs was, respectively, $227.35 and $74.63 per additional arrival <3 hours, $440.72 and $334.09 per additional person with stroke knowledge proficiency, and $655.70 and $811.77 per additional person with preparedness capacity. Using a societal perspective, the ICER for EE versus SC was $84 643 per QALY gained and the ICER for II versus EE was $59 058 per QALY gained. Incorporating fixed costs, EE and II would need to administered to 507 and 1693 or more patients, respectively, to achieve an ICER of $100 000/QALY. CONCLUSION: II was a cost-effective strategy compared with both EE and SC. Nevertheless, high initial fixed costs associated with II may limit its cost-effectiveness in settings with smaller patient populations.

Single- versus multiple-stage catheter-directed thrombolysis for acute iliofemoral deep venous thrombosis does not have an impact on iliac vein stent length or patency rates.

BACKGROUND: Incomplete venous thrombolysis and residual nonstented iliac vein disease are known predictors of recurrent deep venous thrombosis (DVT). Controversy exists as to whether the number of thrombolysis sessions affects total stent treatment length or stent patency. The goal of this study was to evaluate the outcomes of patients who underwent single vs multiple catheter-directed lysis sessions with regard to stent extent and patency. METHODS: Consecutive patients who underwent thrombolysis and stenting for acute iliofemoral DVT between 2007 and 2018 were identified and divided into two groups on the basis of the number of treatments performed (one vs multiple sessions). Operative notes and venograms were reviewed to determine the number of lytic sessions performed and stent information, including size, location, total number, and length treated. End points included total stent length, 30-day and long-term patency, and post-thrombotic syndrome (Villalta score ≥5). The χ2 comparisons, logistic regression, and survival analysis were used to determine outcomes. RESULTS: There were 79 patients who underwent lysis and stenting (6 bilateral interventions; mean age, 45.9 ± 17 years; 48 female). Ten patients (12 limbs) underwent single-stage treatment with pharmacomechanical thrombolysis, and the remaining 69 (73 limbs) had two to four operating room sessions combining pharmacomechanical and catheter-directed thrombolysis. Patients who underwent a single-stage procedure were older and more likely to have a malignant disease. These patients received less tissue plasminogen activator compared with the multiple-stage group (17.2 ± 2.2 mg vs 27.6 ± 11.6 mg; P = .008). Average stent length was 8.8 ± 5.2 cm for the single-stage group vs 9.2 ± 4.6 cm for the multiple-stage group (P = .764). Patients who underwent a single-stage procedure had no difference in average length of stay from that of patients who underwent multiple sessions (8.5 days vs 5.9 days; P = .269). The overall 30-day rethrombosis rate was 7.3%. Two-year patency was 72.2% and 74.7% for the single and multiple stages, respectively (P = .909). The major predictors for loss of primary patency were previous DVT (hazard ratio [HR], 5.99; P = .020) and incomplete lysis (HR, 5.39; P = .014) but not number of procedures (HR, 0.957; P = .966). The overall post-thrombotic syndrome rate was 28.4% at 5 years and was also not associated with the number of treatment sessions. CONCLUSIONS: Single- vs multiple-stage thrombolysis for DVT is not associated with a difference in extent of stent coverage. Patency rates remain high for iliac stenting irrespective of the number of lytic sessions, provided lysis is complete and the diseased segments are appropriately stented.

Fast-track thrombolysis protocol: A single-session approach for acute iliofemoral deep venous thrombosis.

OBJECTIVE: Catheter-directed thrombolysis in the treatment of acute iliofemoral deep venous thrombosis (IFDVT) often requires more than one interventional session to yield successful outcomes. Catheter-directed thrombolysis is generally expensive, requiring prolonged hospital stay that may be associated with increased local and systemic hemorrhagic complications. We developed the fast-track thrombolysis protocol (FTTP) to address these issues. The goal of FTTP is to restore patency during the initial session of thrombolysis, thereby minimizing costs and complications associated with prolonged thrombolysis. METHODS: A retrospective analysis of 38 patients treated for acute IFDVT using FTTP at our institution from January 2014 to February 2019 was performed. The protocol includes periadventitial injection of lidocaine at the venipuncture site under ultrasound guidance, contrast venography of the entire target segment, pharmacomechanical rheolytic thrombectomy of the occluded venous segment, tissue plasminogen activator infusion along the occluded segment, balloon maceration of the thrombus, and, if indicated, venous stent placement in areas of significant (≥50%) stenosis refractory to thrombolysis and balloon angioplasty. Once the thrombus was cleared, patients were prescribed oral antithrombotic therapy. RESULTS: Thirty-eight primary FTTPs (45 total interventions) were performed in 38 patients. The median age was 66 years (range, 39-93 years); 60.5% were female. Initial venous access was most often obtained through the popliteal vein, followed by the femoral and great saphenous veins. The mean operative time was 122 minutes (range, 59-249 minutes), and the median volume of tissue plasminogen activator infused was 10 mg (range, 4-20 mg). The median cost per procedure, including devices and medication, was $5374.45. Median postoperative length of stay was 1 day (range, 1-45 days). Successful single-session FTTP, as determined by completion venography, was accomplished in 81.5% (n = 31/38) of cases. The remaining seven cases (18.5%) required one additional session. Of the 38 patients, 30 (79%) required iliac vein stenting. Periprocedural complications consisted of one patient with retroperitoneal hemorrhage that was managed conservatively. No patients experienced rethrombosis within 30 days of FTTP. During the 5-year study period, there were no cases of pulmonary embolism, significant local or systemic hemorrhage, limb loss, or mortality. CONCLUSIONS: FTTP, as presented herein, appears to be a safe, effective, and cost-effective technique in the resolution of acute IFDVT.

Hospital distance, socioeconomic status, and timely treatment of ischemic stroke.

OBJECTIVE: To determine whether lower socioeconomic status (SES) and longer home to hospital driving time are associated with reductions in tissue plasminogen activator (tPA) administration and timeliness of the treatment. METHODS: We conducted a retrospective observational study using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between January 2015 and March 2017. The study included 118,683 ischemic stroke patients age ≥18 who were transported by emergency medical services to one of 1,489 US hospitals. We defined each patient's SES based on zip code median household income. We calculated the driving time between each patient's home zip code and the hospital where he or she was treated using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA). Outcomes were analyzed using hierarchical multivariable logistic regression models. RESULTS: SES was not associated with OTA (p = 0.31) or tPA administration (p = 0.47), but was associated with the secondary outcomes of onset-to-treatment time (OTT) (p = 0.0160) and in-hospital mortality (p = 0.0037), with higher SES associated with shorter OTT and lower in-hospital mortality. Driving time was associated with tPA administration (p < 0.001) and OTA (p < 0.0001), with lower odds of tPA (0.83, 0.79-0.88) and longer OTA (1.30, 1.24-1.35) in patients with the longest vs shortest driving time quartiles. Lower SES quintiles were associated with slightly longer driving time quartiles (p = 0.0029), but there was no interaction between the SES and driving time for either OTA (p = 0.1145) or tPA (p = 0.6103). CONCLUSIONS: Longer driving times were associated with lower odds of tPA administration and longer OTA; however, SES did not modify these associations.

Innovations in Care Delivery of Stroke from Emergency Medical Services to the Neurointerventional Operating Room.

Acute ischemic stroke (AIS) and its care is currently one of the most dynamic and evolving illnesses across the globe. Among the most crucial factors in providing the best care to patients are the expedient delivery of thrombolytics and endovascular intervention when indicated. Here, we review our unique model of efficient care centered in our innovative Neurological Emergency Department (Neuro ED). The Neuro ED acts as our hub for EMS communication, imaging, administration of intravenous alteplase, and transition to the Neurointerventional OR. Our structure with its enabling of shortened IV alteplase delivery times and faster door-to-needle (DTN) times may serve as an international model for stroke centers.

Pre-thrombectomy intravenous thrombolytics are associated with increased hospital bills without improved outcomes compared with mechanical thrombectomy alone.

OBJECTIVE: To investigate whether significant differences exist in hospital bills and patient outcomes between patients who undergo endovascular thrombectomy (EVT) alone and those who undergo EVT with pretreatment intravenous tissue plasminogen activator (IV tPA). METHODS: We retrospectively grouped patients in an EVT database into those who underwent EVT alone and those who underwent EVT with pretreatment IV tPA (EVT+IV tPA). Hospital encounter charges (obtained via the hospital's charge capture process), final patient bills (ie, negotiated final bills as per insurance/Medicare rates), demographic information, existing comorbidities, admission and discharge National Institutes of Health Stroke Scale (NIHSS) score, and functional independence data (modified Rankin Scale score 0-2) were collected. Univariate and multivariate statistical analyses were performed. RESULTS: Of a total of 254 patients, 96 (37.8%) underwent EVT+IV tPA. Median NIHSS score at admission was significantly higher in the EVT+IV tPA group than in the EVT group (p=0.006). After adjusting for NIHSS admission score, patient bills and encounter charges in the EVT+IV tPA group were still found to be $3861.64 (95% CI $658.84 to $7064.45, p=0.02) and $158 071.29 (95% CI $134 641.50 to $181 501.08, p < 0.001) greater than in the EVT only group respectively. The EVT+IV tPA group had a higher complication rate of intracranial hemorrhage (ICH) (p=0.005). The EVT and EVT+IV tPA groups did not differ significantly in median discharge NIHSS score (p=0.56), functional independence rate at 90 days (p=0.96), or average length of hospital stay (p=0.21). CONCLUSION: Patients treated with EVT+IV tPA have greater hospital encounter charges and final hospital bills as well as higher rates of ICH than patients who undergo treatment with EVT only.

Retrospective comparison of ultrasound facilitated catheter-directed thrombolysis and systemically administered half-dose thrombolysis in treatment of pulmonary embolism.

This study retrospectively compared the outcomes of patients who received ultrasound facilitated catheter-directed thrombolysis (UFCDT) versus systemically administered 'half-dose' thrombolysis (HDT) in 97 patients with PE. The outcomes assessed included changes in baseline pulmonary artery systolic pressure (PASP), right ventricle/left ventricle ratio (RV/LV), cost and duration of hospitalization, death, bleeding, and recurrent venous thromboembolism in the short and intermediate term follow-up. Analyses were performed using a covariance adjustment propensity score approach to address baseline differences between groups in variables associated with PASP and RV/LV, covarying baseline scores. The baseline mean ± SE PASP dropped from 49.3 ± 1.1 to 32.5 ± 0.3 mmHg at 36 hours in the HDT group, and from 50.6 ± 1.2 to 35.1 ± 0.4 mmHg in the UFCDT group; group × time interaction p-value = 0.007. Corresponding drops in the RV/LV were from a baseline of 1.26 ± 0.05 to 1.07 ± 0.01 in the HDT group and from 1.30 ± 0.05 to 1.14 ± 0.01 in the UFCDT group at 36 hours; group × time interaction p-value = 0.269. Statistically significant decreases were noted in PASP and RV/LV for both the HDT and UFCDT at 36 hours and follow-up. PASP through follow-up was significantly lower in the HDT than the UFCDT group. Likewise, RV/LV was lower in the HDT group. The duration and cost of hospitalization were lower in the HDT group (6.2 ± 1.4 days vs 1.9 ± 0.3 days, p < 0.001; US$12,000 ± $3000 vs $74,000 ± $6000, p < 0.001). We conclude that both UFCDT and HDT lead to rapid reduction of PASP and RV/LV, whereas HDT leads to a lower duration and cost of hospitalization.

Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial.

BACKGROUND: Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke. METHODS: We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616. FINDINGS: Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome. INTERPRETATION: Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group. FUNDING: National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.