Acute Therapies Research Articles

Variability and Delay in Telestroke Physician Alert among Spokes in a Telestroke Network: A Need for Metric Benchmarks

Introduction: Telestroke has increased access to acute management of ischemic stroke in areas that lack stroke care expertise, yet delays persist in evaluation and treatment. We describe variation in time to alert a telestroke physician of suspected acute ischemic stroke patients potentially eligible for acute stroke therapies among community hospitals in our telestroke network, and explore demographic and spoke-related characteristics associated with delays. Methods: From our telestroke registry, we identified suspected acute ischemic stroke patients who arrived within 6 hours of symptom onset and underwent video consultation at 1 of 17 community hospitals in our hub-and-spoke network. We compared time between patient arrival to telestroke alert (door-to-page-time) and to tissue plasminogen activator (tPA) administration for eligible patients (door-to-needle-time). We identified factors associated with prolonged metrics. Results: Of 1020 cases between 9/2015 and 3/2017, 47% received tPA. Sixty percent had door-to-page-time more than 15 minutes (median 19.5; IQR, 11-34). Door-to-page-time more than 15 minutes was associated with an 8-fold increase in likelihood of door-to-needle-time more than 60 minutes. Patients with severe stroke experienced faster door-to-page-times. Hospitals with more beds had prolonged door-to-page-time. Full time in-house neurology presence, even when not covering emergent consultations, was associated with faster door-to-page-time over telestroke. Seventy-one percent of patients underwent CT brain prior to the telestroke physician alert; this scenario delayed door-to-page and door-to-needle times. Conclusions: Door-to-page-time varied considerably among spokes. Awaiting CT scan prior to alerting the telestroke consultant of a stroke code delayed metrics. Telestroke physician alert standards are needed, as are educational initiatives on acute ischemic stroke management and workflow.

Outcomes measures in children after acute central nervous system infections and malaria.

Acute central nervous system (CNS) infections in children result in significant mortality and neurologic morbidity worldwide. This article summarizes the recent pediatric literature published on outcomes measures used after acute infectious meningitis, encephalitis, and cerebral malaria, and highlights ongoing research efforts to standardize outcomes measurements. Search terms were geared toward functional, cognitive, behavioral, and other outcome assessments. Recent data suggest that, depending on microbiological cause, there are differences in currently used outcome measures following acute CNS infections. Outcomes assessments include a variety of formal psychological tests (structured interviews and neuropsychological tests of cognitive and motor functioning) and dichotomized or ordinal scales. Standardization of outcome measures, however, is lacking. Global efforts to standardize outcomes that encompass both the child and family are ongoing. Centers worldwide can track and measure a variety of cognitive, behavioral, and functional outcomes after acute CNS infections. Standardized documentation and coding of clinically important outcomes is needed. Further research to evaluate effective practices using acute adjunctive and rehabilitation therapies will be aided by outcome measure standardization.

Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications

BackgroundThere is a significant unmet need for new, effective and well tolerated acute migraine treatments. A recent study has demonstrated that a novel remote electrical neuromodulation (REN) treatment provides superior clinically meaningful pain relief with a low rate of device-related adverse events. The results reported herein compare the efficacy of REN with current standard of care in the acute treatments of migraine.MethodsWe performed a post-hoc analysis on a subgroup of participants with migraine from a randomized, double-blind, parallel-group, sham-controlled, multicenter study on acute care. The original study included a 2–4 weeks run-in phase, in which migraine attacks were treated according to patient preference (i.e., usual care) and reported in an electronic diary; next, participants entered a double-blind treatment phase in which they treated the attacks with an active or sham device. The efficacy of REN was compared to the efficacy of usual care or pharmacological treatments in the run-in phase in a within-subject design that included participants who treated at least one attack with the active REN device and reported pain intensity at 2 h post-treatment.ResultsOf the 252 patients randomized, there were 99 participants available for analysis. At 2 h post-treatment, pain relief was achieved in 66.7% of the participants using REN versus 52.5% participants with usual care (p < 0.05). Pain relief at 2 h in at least one of two attacks was achieved by 84.4% of participants versus 68.9% in usual care (p < 0.05). REN and usual care were similarly effective for pain-free status at 2 h. The results also demonstrate the non-inferiority of REN compared with acute pharmacological treatments and its non-dependency on preventive medication use.ConclusionREN is an effective acute treatment for migraine with non-inferior efficacy compared to current acute migraine therapies. Together with a very favorable safety profile, these findings suggest that REN may offer a promising alternative for the acute treatment of migraine and could be considered first line treatment in some patients.Trial registrationClinicalTrials.gov NCT03361423. Registered 18 November 2017.

Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review.

To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5-HT1F receptor agonists (ditans). Current acute migraine therapy consists of nonspecific analgesia and triptans. Limitations to these medicines, including lack of efficacy in many patients, side effects and the contraindication of triptans in patients with cardiovascular disease, suggest that there is an unmet need for new treatments. Studies of serotonin pharmacology led to the development of triptans, 5-HT1B/1D receptor agonists, some of which have actions at the 5-HT1F receptor. Exploration of the role of calcitonin gene-related peptide (CGRP) has resulted in the development of CGRP receptor antagonists. The authors performed a literature search of Pubmed and Cochrane databases as well as reviewed abstracts presented at meetings: American Headache Society, American Academy of Neurology, European Headache Federation and the Migraine Trust International Symposium, as well as on-line sources. The authors briefly detail the relevant migraine pathophysiology pertaining to 5-HT1F receptor and the CGRP pathway relevant to acute therapies. Recent clinical trials of acute therapies in which 5-HT1F receptor agonists or CGRP receptor antagonists were studied are summarized. Two 5-HT1F receptor agonists have reached phase II clinical trials. One, lasmiditan, has completed 2 phase III clinical trials, demonstrating a significant effect for pain freedom and most bothersome symptom at 2 hours. Among the 6 gepants tested for the acute treatment of migraine to date, after issues for some of hepatic safety or efficacy, 2 CGRP receptor antagonists, rimegepant and ubrogepant, have completed phase III trials showing efficacy and safety. Current available therapies have either been nonspecific or had important limitations, including in patients with cardiovascular risk factors. Phase III clinical trials of lasmiditan, rimegepant and ubrogepant all met their primary endpoints, so the options for migraine-targeted acute therapy will likely soon increase.

122 ‘My migraine voice: burden of migraine and it’s management in an australian cohort’

IntroductionMigraine is the greatest cause of disability under the age of 50. It impairs ability to function, work and maintain relationships. This survey aimed to assess the impact of migraine and its management.MethodsA questionnaire was sent to patients &gt;18 years old who had taken at least one preventive treatment for migraine in the past. We report here the Australian results.Results68% were women, mean age 41 years. 53% were in paid employment whilst 13% received a disability allowance due to migraine. All patients (n=320) in the Australian survey had ≥ 4 migraine days each month. 90% had taken at least one preventive (274), with 80% (194) needing to change the preventive treatments previously. Common comorbidities were depression (41%), anxiety (40%), chronic pain (29%), sleep disorder (25%) and overweight (24%).Diagnosis rate on initial GP visit was 57%, with 26% receiving a diagnosis in &lt;1 month and 55% by 6 months.There was greater retention of use (60%) and satisfaction (60%) with acute therapies, compared with use (43%) and satisfaction (53%) with preventives. Dissatisfaction with preventives included lack of efficacy (54%) and too many side effects (36%). Most (&gt;60%) patients reported fear of the next attack, feeling hopeless and difficulty thinking clearly during attacks. Employers were often (69%) aware of the migraines, but only 24% offered any support. Migraine had negative impacts on relationships.ConclusionThe Migraine Voice Survey highlights the true burden of migraine in Australia and limitations of current management options.

132 Brushstrokes after stroke – art and neuroplasticity

IntroductionDespite current developments in acute stroke therapies, 65% of stroke patients have varying degrees of disability. Whilst focus on acute stroke reperfusion strategies is vital, stroke survivors still need support and appropriate opportunities for rehabilitation.Methods and resultsThis is an inspiring story of an 86-year old patient with locked in syndrome who rediscovered her artistic talent after a disabling stroke. She presented with right hemiparesis, bilateral ptosis, ophthalmoplegia and aphasia. Her MRI showed multiple infarcts affecting the midbrain, thalamic, cerebellar and occipital regions. There was stenosis of the right vertebral artery- the left was hypoplastic, and new atrial fibrillation was detected.There was no response to early rehabilitation strategies and her husband decided to care for her at home. He used creative strategies to encourage motor skills and participation in daily activities, and despite never regaining speech or independent mobility, she was able to interact meaningfully with him and her environment. They enjoyed a full and active life until her demise last year.The patient was an accomplished artist and, with the help of her husband, reengaged in painting. This resulted in an original collection of paintings that formed an exhibition in Wollongong Art Gallery.ConclusionThis is a life affirming story of love, enablement and ingenuity after disabling strokes, and a reminder that neuroplasticity can occur at any age. Art can provide a way to harness neuroplasticity to improve neurological deficits and quality of life, even despite significant disability. ‘A man paints with his brains and not with his hands. ‘(Michaelangelo).

Sixty years in the making: collagenase Clostridium histolyticum, from benchtop to FDA approval and beyond.

The introduction of collagenase Clostridium histolyticum (CCH) as the first and only FDA-approved non-surgical treatment for Peyronie's disease (PD) has been an important step in its management. Our aim is to provide an overview of the historical origins of CCH and its development through FDA approval and beyond for the treatment of PD. A PubMed search using the terms Peyronie OR Peyronie's AND collagenase and limited to clinical research studies resulted in 24 articles that were examined for the current review. PD is a connective tissue disorder of the penile tunica albuginea involving fibrotic penile plaques that cause abnormal curvature and, in many cases, erectile pain. Although the exact mechanism and underlying pathophysiology are not well characterized, the known lability of these plaques to exogenous bacterial collagenase combined with a lack of effective medical therapies led to the development of CCH as an evidence-based treatment of PD. The initial discovery of collagenase was followed by in vitro studies on PD plaque tissue and following the phase 3 IMPRESS trial culminated in FDA approval of CCH in 2013. Future directions in CCH therapy include improved patient selection, use in acute phase PD, adjuvant and combination therapies, and novel delivery mechanisms. CCH provides an effective non-surgical treatment option for men with PD. We have traced the development of CCH in the treatment of PD from the earliest in vitro investigations to comprehensive multi-study meta-analyses confirming its highly rated efficacy when compared to other historical non-surgical remedies.

Temporal Trends in the Use of Acute Recanalization Therapies for Ischemic Stroke in Patients with Cancer

Objective: We sought to characterize the US nationwide temporal trends in recanalization therapy utilization for ischemic stroke among patients with and without cancer. Methods: We identified all acute ischemic stroke (AIS) hospitalizations in the National Inpatient Sample from January 1, 1998 to September 30, 2015. The primary exposure was solid or hematologic cancer. The primary outcome was use of intravenous thrombolysis. The secondary outcome was use of endovascular therapy (EVT). Results: Among 9,508,804 AIS hospitalizations, 503,510 (5.3%) involved cancer patients. Intravenous thrombolysis use among ischemic stroke patients with cancer increased from .01% (95% confidence interval [CI], .00%-.02%) in 1998 to 4.91% (95% CI, 4.33%-5.48%) in 2015, whereas intravenous thrombolysis use among ischemic stroke patients without cancer increased from .02% (95% CI, .01%-.02%) in 1998 to 7.22% (95% CI, 6.98%-7.45%) in 2015. The demographic- and comorbidity-adjusted odds ratio/year of receiving intravenous thrombolysis was similar in patients with cancer (1.21; 95% CI, 1.20-1.23) versus those without (1.20; 95% CI, 1.19-1.21). EVT use among ischemic stroke patients with cancer increased from .05% (95% CI, .02%-.07%) in 2006 to 1.90% (95% CI, 1.49%-2.31%) in 2015, whereas EVT use among ischemic stroke patients without cancer increased from .09% (95% CI, .00%-.18%) in 2006 to 1.88% (95% CI, 1.68%-2.09%) in 2015. Conclusions: Among 9.5 million AIS hospitalizations, patients with cancer received intravenous thrombolysis about two thirds as often as patients without cancer. This difference persisted over time despite increased utilization in both groups. EVT utilization was similar between cancer and non–cancer AIS patients.

Workflow Optimization for Ischemic Stroke in a Community-Based Stroke Center

We analyzed the effect of specific optimization steps to reduce treatment delays in a nonacademic stroke hospital setting. The data from patients with ischemic stroke who had been treated with intravenous tissue plasminogen activator or endovascular therapy, or both, were analyzed. The metrics were divided into 2 periods: preoptimization period (October 1, 2015 to September 30, 2016) and postoptimization period (October 1, 2016 to September 30, 2017). The key interventions were 1) notification by the emergency medical service to the emergency department and stroke team; 2) division of the stroke alert between level 1 (intravenous/intra-arterial candidate) and level 2; 3) direct transportation of level 1 patients to brain computed tomography; 4) limitation of nonessential interventions; 5) stroke orientation; 6) 24-hour, 7-day code stroke response by a vascular neurologist; 7) earlier notification of the interventional radiology team; 8) direct transportation from computed tomography to angiography suite for large vessel occlusion; and 9) multidisciplinary monthly meetings to discuss delayed cases. A total of 279 patients were identified. No significant differences in any of the baseline characteristics were documented. Almost all metrics favored the postoptimization period, with remarkable improvement in the door-to-puncture time (median, 64 minutes; interquartile range, 36-86; vs. 47 minutes; interquartile range, 20-62; P= 0.001). We observed an increased percentage of good clinical outcomes in the postoptimization group (60.1% vs. 54.8%; P= 0.500). We found an 8.4% increase in patients with good clinical outcomes in the postoptimization group compared with our previously reported work. For acute reperfusion therapies, significant reductions in workflow intervals can be achieved after simple optimization methods in a nonacademic community-based hospital.

Impact of Leukoaraiosis Severity on the Association of Time to Successful Reperfusion with 90-Day Functional Outcome After Large Vessel Occlusion Stroke.

The chance for a favorable outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke decreases with the symptom onset-to-reperfusion time (OTR). Patients with severe leukoaraiosis are at increased risk for a poor outcome after MT. However, whether leukoaraiosis modulates to the association between OTR and 90-day functional outcome is uncertain. We retrospectively analyzed 144 consecutive patients with successful (TICI ≥ 2b/3) MT for anterior circulation large vessel occlusion within 24h form OTR between January 2012 to November 2016. Leukoaraiosis was dichotomized to absent-to-mild (van Swieten scale score 0-2) versus moderate-to-severe (3-4) as assessed on admission head CT. Multiple linear, logistic, and ordinal regression analyses were used to determine the association between leukoaraiosis, OTR, and 90-day modified Rankin Scale (mRS) score, after adjustment for pertinent covariates. Leukoaraiosis was independently associated with theOTR on multivariable linear regression (p = 0.003). The association between OTR and 90-day outcome depended on the degree of pre-existing leukoaraiosis burden as shown by a significant leukoaraiosis-by-OTR interaction on multivariable logistic regression (OR 0.76, 95% CI 0.58-0.98, p = 0.037) and multivariable ordinal regression (OR 0.87, 95% CI 0.78-0.97, p = 0.011). Pre-existing leukoaraiosis is associated with the 90-day functional outcome after successful reperfusion and impacts the association between the OTR and 90-day mRS among patients undergoing MT. Patients with high leukoaraiosis burden need to present earlier than patients with low leukoaraiosis burden for a similar favorable outcome. Pending confirmation, these results may have important implications for optimizing patient selection for acute stroke therapies.

It is more than transportation time only: "Drip and ship" delays endovascular thrombectomy in stroke

Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are acute therapies approved for ischemic stroke. In Germany there are approximately 110 supra-regional stroke units with and approximately 200 regional stroke units without 24 / 7 EVT. Regional stroke units must cooperate with supra-regional stroke units in order to offer EVT if indicated. In the current paper, we discuss the time delay due to secondary transportation from regional to supra-regional stroke units. Acute stroke therapy of all patients treated at the regional stroke unit of the SRH Clinics in Sigmaringen in 2016 was analysed retrospectively. Sigmaringen cooperates with the supra-regional stroke units of the Oberschwabenklinik Ravensburg and the University Hospital Tübingen. A total of 299 patients with ischemic stroke and 168 patients with transient ischemic attack (TIA) were treated at the Sigmaringen stroke unit. Of these, 52 patients received IVT and 21 patients were transferred for EVT; of these, 15 patients actually underwent EVT after their cases were reviewed. The CT-to-Groin-times were more than double as long as compared to those in patients directly admitted to the supra-regional stroke units (median 180 minutes vs. 88 minutes). Primary admission of patients with acute stroke to regional stroke units without EVT prolongs the CT-to-Groin time. Implications of this knowledge on current and future patient care structures are discussed.

Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B.

BackgroundGlobally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy.Methodology/Principal findingsFrom 2013–2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups.Conclusions/SignificanceThese findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.

Do Antithymocyte Globulin-Free Acute Rejection Therapies Increase the Risk of Polyoma Nephropathy in Renal Transplant Recipients?

IntroductionBK virus nephropathy is a serious complication that can lead to allograft kidney loss. Excessive immunosuppression increases the risk. We aimed to evaluate whether there is an increased risk of BK viremia and nephropathy in patients who underwent high-dose immunosuppression because of the development of acute rejection in the early period after kidney transplantation. MethodsThis retrospective cohort study was performed between April 2015 and March 2016. Twenty-nine patients who had biopsy-proven acute rejection in the first 3 months were evaluated for BK viremia and nephropathy. Thirty patients who had transplantations at the same period were the control group. Plasma BK-DNA values were examined at 1, 2, 3, 6, 9, and 12 months after the rejection treatment and at 3, 6, 9, and 12 months in the control group. Presence of polyoma nephropathy was examined with surveillance biopsies at the 6 and 12 months. ResultsAcute rejection treatment was started on the 12th day after transplantation (2–37 days). Seventeen cellular rejections and 12 humoral rejections were reported by biopsy. Two of the 12 humoral rejections were suspicious. Only pulse steroid (PS) (n = 18); PS, plasmapheresis, and intravenous immunoglobulin (n = 8); PS and intravenous immunoglobulin (n = 2); and PS and plasmapheresis (n = 1) treatments were performed. In 21 patients in the rejection group and 25 patients in the control group, BK-DNA was not positive at all. Two patients had graft loss at 11 and 36 months in the rejection group. Graft losses were secondary to rejection. ConclusionsTreatment with antithymocyte globulin-free regimens after acute rejection episodes did not lead to an increase in BK viremia.

Identification of children with anaphylaxis at low risk of receiving acute inpatient therapies.

ObjectiveOpportunity exists to reduce unnecessary hospitalizations for children with anaphylaxis given wide variation in admission rates across U.S. emergency departments (EDs). We sought to identify children hospitalized with anaphylaxis at low risk of receiving epinephrine and other acute inpatient therapies, as these patients may be candidates for ED discharge rather than inpatient hospitalization.MethodsWe conducted a single-center retrospective cohort study of children 1–21 years of age hospitalized with anaphylaxis from 2009 to 2016. Acute inpatient therapies included intramuscular (IM) or racemic epinephrine, bronchodilators, fluid boluses, vasopressors, non-invasive ventilation, or intubation. We derived age-specific (pre-verbal [<36 months] vs. verbal [≥ 36 months]) prediction rules using recursive partitioning to identify children at low risk of receiving acute inpatient therapies.ResultsDuring the study period 665 children were hospitalized for anaphylaxis, of whom 108 (16.2%) received acute inpatient therapies. The prediction rule for patients < 36 months (no wheezing, no cardiac involvement [hypotension or wide pulse pressure]) had a sensitivity of 90.5% (CI 69.6–98.8%) and a negative predictive value of 98.3% (CI 94.1–99.8%) for identifying children at low risk of receipt of acute inpatient therapies during hospitalization. For children ≥ 36 months, the prediction rule (no wheezing, no cardiac involvement, presence of gastrointestinal symptoms) had a sensitivity of 90.8% (CI 82.7–96.0%) and a negative predictive value of 92.4% (CI 85.6–96.7%).ConclusionsWe derived age specific prediction rules for children hospitalized with anaphylaxis at low risk of receiving epinephrine and other acute inpatient therapies. These children may be candidates for ED discharge rather than inpatient hospitalization.

Sixth Kraepelin Symposium-Understanding and Treating Cognitive Impairment and Depression in Schizophrenia and Affective Disorders.

The Sixth Kraepelin Symposium was held at the Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich in October 2018, covering reports from 12 working groups (Keith H. Nuechterlein, Ph.D., University of California, Los Angeles; Kim T. Mueser, Ph.D., Center for Psychiatric Rehabilitation, Boston University, U.S.A.; Dominic Dwyer, Ph.D, Hospital LMU, Munich; David Fowler, Ph.D. University of Sussex, Brighton, U.K.; Martin Hautzinger, Ph.D., University of Tübingen; Nikolaos Koutsouleris, M.D., Hospital LMU, Munich; Stephan Leucht, M.D., Technical University Munich, Munich; David Miklowitz, Ph.D., UCLA School of Medicine, Los Angeles. U.S.A.; Cornelius Schüle, M.D., Hospital LMU, Munich; Florian Seemüller. M.D., kbo-Lech-Mangfall Clinics for Psychiatry and Psychotherapy, Garmisch Partenkirchen; Carla Torrent, Ph.D., Institute of Neuroscience, University of Barcelona, Barcelona, Spain.) from the United States and Europe on understanding and treating cognitive impairment and depression in schizophrenia and affective disorders. Current psychological interventions to improve outcome in schizophrenia and affective disorder such as cognitive remediation, illness management, psychoeducational and cognitive therapy were focused on, as were evidence-based psychological and pharmacological treatment options, guidelines for treating cognitive deficits and depression in schizophrenia, Cochrane-meta-analysis of acute therapies, relapse prevention as well as supported withdrawal from medication. Prevention of cognitive dysfunction and symptom exacerbation was approached in terms of machine learning methods to revisit Kraepelin's illness distinctions, application of new strategies in order to increase the rate of social recovery in patients with first-episode psychosis as well as in terms of state of the art psychosocial interventions for bipolar disorder in adolescents. Finally, the dissemination of information to consumers and the contribution to the reduction of stereotypes in psychiatry was also part of the symposiums aims.

Abstract TP268: Utilization and Appropriateness of Emergency Medical Services Air Transport in Acute Ischemic Stroke Care

Introduction: Although air (helicopter) transfer is largely accepted as improving outcomes in time sensitive conditions including acute ischemic stroke (AIS), inappropriate triage of these patients when they are ineligible for acute stroke therapies places patients and providers at unnecessary risk and wastes limited healthcare resources. Extension of the endovascular therapy time window to twenty-four hours further increases the burden on stroke systems of care. As the tertiary flagship institution and only comprehensive stroke center (CSC) in a rural state, we sought to identify how accurate our triage system was at identifying ischemic stroke patients appropriate for air transfer. Hypothesis: A significant percent of AIS patients inappropriately utilize HelicopterEmergency Medical Services (HEMS). Based on information known prior to transfer, the majority are avoidable. Methods: We defined inappropriate utilization basedon time from last known normal (LKN), stroke severity and baseline functional status. A retrospective chart review was performed on all stroke alerts that arrived at our hospital by HEMS in 2017. Results: Of the 141 acute stroke patients transferred by HEMS, 23 (16%) were deemed inappropriate; 14 (61% ) were outside the acute treatment time windows for either IV tPA or Endovascular Therapy (EVT); 5(22%) were ineligible for EVT (NIHSS&lt;6); 2 (9%) were ineligible for EVT (mRS≥3); and 2 (9%) were flown despite negative angiographic studies performed at transferring institution. At an average cost of $18,500/flight, $425,500 in total was attributed to inappropriate transport. Thirteen (57%) of the patients were interfacility transfers where the decision to arrange HEMS occurred after a physician’s evaluation. Conclusion: HEMS transport for AIS patients plays a crucial role in delivering the best care. However, a significant percent of patients do not meet criteria for its appropriate utilization, most commonly when pre-established LSN are outside of acute treatment windows. Furthermore, inappropriate transfers were initiated in spite of outside hospital physician evaluation over 50% of the time. These results represent a unique opportunity to coordinate education and buildeffective triage paradigmsacross a system of stroke care.

Abstract 140: Impact of Stroke Nurse Education on Stroke Team Activations and Reperfusion Treatments in a Large Regional Stroke Care Network

Introduction: Nurse Education is an important component of successful acute stroke treatment networks. We sought to describe the impact of educational events on the number of acute stroke activations and acute stroke reperfusion therapies, as well as the sustainability of any effects seen within our large network. Methods: In 2016, 40 educational events were performed at 14 hospitals within the Greater Cincinnati Stroke Network. Nurses from every unit were encouraged to attend with a focus on the Emergency Department. A one hour presentation titled “Overview and Acute Management of Stroke” was given at each event, which included when to activate the stroke team, identifying the effects of time on the brain during stroke, and strategies for treating patients faster. The number of calls and treatments in the network within the stroke team call log during 2016 were analyzed, partial years before and after 2016 were also analyzed to evaluate 6-months before and after each education event. A segmented Poisson regression model was used to estimate the change in weekly number of calls and treatments immediately after the first education event and the change in the trend over time. Results: In 2016, the network received 4273 stroke calls from 39 hospitals, with 457 reperfusion treatments. Among the 14 hospitals that held an education event, we found that the number of calls went up by 40% immediately after the event (p&lt;0.01). Although we also saw a jump in the number of treatments by 46% after, this was not statistically significant (p=0.16). At 6-months, the number of calls was 8% higher than the projected rate without the education (Figure). Discussion: Network wide Nurse Education was associated with a significant and profound increase in stroke activations, with a concomitant non-significant increase in reperfusion treatments. This effect was sustained out to 6 months after the educational event. Nurse Education is critical in maintaining networks and improving stroke care delivery.

Abstract TP352: Work Flow Optimization in Acute Stroke Therapy in a Community Based Comprehensive Stroke Center

Background and Purpose: In acute stroke therapy, faster reperfusion leads to better outcome. We analyzed optimization steps to reduce treatment delays at a comprehensive stroke center in a non-academic tertiary hospital. Methods: Consecutive patients with ischemic stroke treated with either IV tPA, endovascular therapy or both were analyzed. Patient metrics were divided into two periods: pre-optimization period and post-optimization period. Key interventions of this workflow included: (1) addition of pre notification by EMS to ER and stroke team; (2) dividing stroke alert to level 1 (potential IV/IA candidate) vs. level 2; (3) direct transportation of level 1 stroke patients to brain CT imaging; (4) limitation of non-essential interventions; (5) 24/7 code stroke response by an in house trained vascular midlevel (NP/PA) and vascular neurologist (either in house or through telestroke network);(6) earlier notification of IR team; (7) CT to angiosuite direct transportation for LVO; (8) multidisciplinary monthly meetings to discuss delayed cases. Door to needle time and door to puncture time were used as target metrics in order to measure improvement. Results: A total of 279 patients were identified (101 in the pre-optimization and 178 in the post- optimization periods). No significant differences in any of the patient’s baseline characteristics were documented in the two observation periods. Almost all metrics favored the post-optimization period with a remarkable improvement in door to puncture time (64 (IQR 36-86) vs. 47 (IQR 20-62) min, p=0.002). Although non-statistically significant, we observed an increased percentage of good clinical outcomes in the post-optimization group (60.1% vs 54.8%, p=0.500). Conclusions: For patients undergoing acute reperfusion therapies, significant reductions in workflow time-frames can be achieved after simple optimization steps in a non-academic community based hospital.

Abstract TMP83: Long-term Clinical and Health Economic Consequences of Worsened Post-stroke Status in Patients With Pre-morbid Disability

Background: Patients with pre-morbid disability – generally defined as modified Rankin Scale score (mRS)≥2 – are often excluded from trials of acute stroke therapies. However, increased disability in such patients will adversely affect long-term outcomes if treatments are withheld in routine practice. We assessed the extent to which increased disability post-stroke influences 5-year mortality, institutionalization, and costs in pre-morbidly disabled patients. Methods: In a population-based, prospective cohort of ischaemic stroke patients (Oxford Vascular Study, 2002-2014), we tracked mortality, institutionalization, and health/social-care costs during follow-up. We compared 5-year mortality and/or post-stroke institutionalization (Cox regressions), and 5-year health/social-care costs (generalized linear model) in 3-month survivors with pre-morbid mRS 2-4 (excluding extreme disability, mRS=5), based on degree of change in mRS(ΔmRS) from pre-stroke to 3-months post-stroke, adjusting analyses for age/sex/initial NIHSS. Results: Among 1,607 patients, 530(33.0%) had pre-morbid mRS=2-4. Only 2 pre-morbidly disabled patients received thrombolysis, but 421(79.4%) were alive at 3-months. ΔmRS was independently associated with 5-year mortality/institutionalization (aHR for ΔmRS=1 vs 0: 1.59,1.20-2.11; ΔmRS=2: 2.39,1.62-3.53; ΔmRS=3: 4.12,1.98-8.60,p&lt;0.001) and costs (margin for ΔmRS≥2 vs 0: $30,011, 95%CI $4,222-55,801,p=0.023). Results were similar on examining patients with pre-morbid mRS 2, 3, 4 separately (e.g. 5-year mortality/institutionalization aHR for pre-morbid mRS=3 with ΔmRS=1 vs 0: 1.60,1.06-2.42,p=0.027; ΔmRS=2: 3.20,1.85-5.54,p&lt;0.001). Conclusions: Stroke patients with pre-morbid disability have higher mortality, institutionalization, and costs if they accumulate additional disability due to the stroke. These findings highlight the long-term outcomes expected if acute interventions are routinely withheld in patients with mild-moderate pre-morbid disability, and suggest that trials/registries should include such patients.

Abstract WP64: The Effect of Leukoaraiosis on Functional Outcome After Thrombectomy

Introduction: The chance for a favorable outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke decreases with the symptom onset-to-reperfusion time (OTR). Patients with severe leukoaraiosis are at increased risk for a poor outcome after MT. However, whether leukoaraiosis modulates to the association between OTR and 90-day functional outcome is uncertain. Methods: We retrospectively analyzed 144 consecutive patients with successful (TICI ≥2b/3) MT for anterior circulation LVO within 24 hours form OTR between January 2012 to November 2016. Leukoaraiosis was dichotomized to absent-to-mild (van Swieten scale score 0-2) versus moderate-to-severe (3-4) as assessed on admission head CT. Multiple linear, logistic, and ordinal regression analyses were used to determine the association between leukoaraiosis, OTR and 90-day modified Rankin Scale (mRS) score, after adjustment for pertinent covariates. Results: Leukoaraiosis was independently associated with OTR on multivariable linear regression ( p =0.003). The association between OTR and 90-day outcome depended on the degree of preexisting leukoaraiosis burden as shown by a significant leukoaraiosis-by-OTR interaction on multivariable logistic regression (OR 0.76, 95%-CI 0.58-0.98, p =0.037) and multivariable ordinal regression (OR 0.87, 95%-CI 0.78-0.97, p =0.011). Conclusions: The severity of pre-existing leukoaraiosis is associated with 90-day functional outcome and modulates the association between the OTR and 90-day mRS among patients undergoing MT within 24 hours from last known well. If confirmed, our results may have important implications for optimizing patient selection for acute stroke therapies.