American Heart Association


Utility Weighted Modified Rankin Scale and the Future of Patient-Centered Outcomes in Stroke Research

Kevin S. Attenhofer, MD

Dijkland SA, Voormolen DC, Venema E, Roozenbeek B, Polinder S, Haagsma JA, et al. Utility-Weighted Modified Rankin Scale as Primary Outcome in Stroke Trials: A Simulation Study. Stroke. 2018

As stroke neurologists, we are all intimately familiar with the modified Rankin Scale (mRS) as a measure of degree of disability. It is a common outcome measure in stroke research and can be statistically analyzed as a simple dichotomization or ordinal shift (among other options). The dichotomized outcome takes varied and complex neurological outcomes and simplifies them down to nominal variables of “good” or “bad.” This is statistically more straightforward, but does result in some outcome information being discarded. The ordinal shift retains more of this information, but typically requires larger sample size to maintain adequate power. Even when well powered, however, the mRS still has a disproportionate focus on motor function when compared to other neurological domains, such as cognition or patient metrics such as quality of life.

Insights from Modeling Stroke Systems of Care in Philadelphia

Neal S. Parikh, MD

Mullen MT, Pajerowski W, Messe SR, Mechem CC, Jia J, Abboud M, et al. Geographic Modeling to Quantify the Impact of Primary and Comprehensive Stroke Center Destination Policies. Stroke. 2018

Dr. Mullen and colleagues performed a geographic modeling study to understand the implications of several pre-hospital triage strategies on transport times. The rationale for this and related studies is that optimizing stroke systems of care requires accounting for regional and local constraints. Because most of the U.S. population lives in urban areas, investigating urban stroke systems of care is worthwhile.

Philadelphia has only one EMS provider. So, the researchers were able to use EMS data to identify and geocode all ambulance-transported patients with possible stroke and then use a maps application programming interface (API) to estimate travel times. They also had actual travel times as reported by EMS.

The PLUMBER Study Yields an Important Piece of the Stroke Systems of Care Puzzle

Neal S. Parikh, MD 

Dozois A, Hampton L, Kingston CW, Lambert G, Porcelli TJ, Sorenson D, et al. PLUMBER Study (Prevalence of Large Vessel Occlusion Strokes in Mecklenburg County Emergency Response). Stroke. 2017

Optimizing access to endovascular therapy has become a public health priority. While various national guidelines seek to shape acute stroke EMS triage practices broadly, regulatory bodies have also acknowledged the need to tailor protocols to local and regional environments.

In deciding whether to triage an individual patient with suspected stroke to an endovascular center instead of a primary stroke center, EMS may consider factors such as relative travel distances, stroke severity, and the likelihood of a large vessel occlusion (LVO).

LVO screening tools have inherent imprecision, and the positive predictive value, of course, depends on the prevalence of LVO. For this reason, knowing the prevalence of LVO among acute ischemic stroke 9-1-1 dispatches is of importance. Further, at an organizational level, the accuracy and precision of LVO detection in the field has upstream implications for case load at endovascular and non-endovascular centers. The importance of these considerations varies by locale.

Cost Effectiveness and Analysis of Mechanical Thrombectomy for Acute Ischemic Stroke

Sami Al Kasab, MD

Sevick LK, Ghali S, Hill MD, Danthurebandara V, Lorenzetti DL, Noseworthy T, et al. Systematic Review of the Cost and Cost-Effectiveness of Rapid Endovascular Therapy for Acute Ischemic Stroke. Stroke. 2017

Stroke remains one of the most devastating neurological illnesses and the leading cause of long-term disability in the U.S. It’s projected that the total cost of stroke from 2005 to 2050 will be $1.52 trillion for non-Hispanic whites, $313 billion for Hispanics, and $379 billion for African Americans. Until 2015, intravenous alteplase (rtPA) was the only proven treatment for acute ischemic stroke. In 2015, a series of five randomized controlled trials demonstrated the effectiveness of mechanical thrombectomy for patients presenting with acute ischemic stroke due to anterior circulation large vessel occlusion within 6 hours of symptom onset.

In this study, Sevick et al perform a systematic review to evaluate cost effectiveness of endovascular therapy (EVT) for acute ischemic stroke. The authors also aim to synthesize all the publicly available economic literature regarding EVT.

Benchmarking Telestroke Proficiency

Abbas Kharal, MD, MPH, and Richa Sharma, MD, MPH

Jagolino-Cole AL, Bozorgui S, Ankrom CM, Bambhroliya AB, Cossey TD, Trevino AD, et al. Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular Fellows and Attendings. Stroke. 2017

Telestroke management is built into the curriculum of many vascular neurology fellowships and affords fellows (NVF) the opportunity to achieve proficiency in this modality. This study demonstrates that the page-to-needle time, or PTNT, is higher among NVFs compared to NVAs. As a result, the authors are suggesting that PTNT is a metric of proficiency. Given lower PTNT among NVAs compared to NVFs, there is an assumption that further training may decrease PTNT and, transitively, increase proficiency. As such, there may be a benefit in greater emphasis of dedicated telestroke training during fellowship.

There is an inherent truth in the logic that additional training can result in decreased PTNT just by sheer procedural repetition to learn the logistics of data-gathering by the phone, video, and imaging from an outside institution. However, perhaps the process is also faster for NVAs compared to fellows due to the attendings’ greater body of experiences seeing numerous patients with each stroke syndrome, treating them acutely, and then following the clinical course in the rehabilitation and subacute phase. Thus, proximal care of stroke patients longitudinally may aide in faster decision-making for remote, telestroke patients. Given that most vascular neurology fellowships are only one clinical year, it is thus critical that telestroke training does not supersede rotations, which require direct patient contact throughout the spectrum of the disease, since it is this contact which informs the decision-making process in the practice of telestroke.

Beyond Drip and Ship: The Role of Baseline Vascular Imaging for Referring Hospitals in Acute Ischemic Stroke Triage for the Endovascular Era

Danny R. Rose, Jr. MD

Boulouis G, Siddiqui K, Lauer A, Charidimou A, Regenhardt R, Viswanathan A, et al.  Immediate Vascular Imaging Needed for Efficient Triage of Patients With Acute Ischemic Stroke Initially Admitted to Nonthrombectomy Centers. Stroke. 2017

The landmark publication of multiple positive endovascular thrombectomy (EVT) trials in 2015 was a pivotal moment for treatment of acute ischemic stroke. The most significant development in acute stroke treatment in the nearly twenty years since the FDA approval of tissue plasminogen activator in 1996 has led to much discussion with respect to improving stroke systems of care to be able to provide this treatment to as many eligible patients as possible. Reflecting this new development in acute stroke treatment, the American Heart Association released a focused update to their guidelines on acute stroke treatment that recommended endovascular therapy be offered to patients who present within 6 hours of last known normal and have a favorable imaging profile and a National Institutes of Health Stroke Scale (NIHSS) of 6 or greater.

Just as the time-sensitive nature of intravenous thrombolytic administration led to the development of prehospital stroke scales and the stroke alert process, the most effective way to triage and treat patients with suspected emergent large vessel occlusions (LVO) amenable to endovascular treatment is a topic of ongoing research and debate. An important facet of this discussion concerns the most effective method to triage and transfer patients with suspected LVO to a thrombectomy-capable stroke center. A cohort by Sarraj et al. presented at the 2017 International Stroke Conference showed comparably good outcomes for patients transferred to thrombectomy-capable centers as compared to patients who presented directly to the facility, suggesting that the “drip and ship” transfer paradigm can be successfully augmented to accommodate endovascular therapy.

Structured Nurse Practitioner Transitional Stroke Program Reduced 30-day Readmissions after Stroke

Qing Hao, MD, PhD

After discharge from hospital, strokes survivors usually are faced with physical and cognitive impairments, complex medication regimen, new diagnosis of other medical illness and need of social support which all significantly affect stroke recovery and readmissions due to stroke related complications or other medical conditions. The experience from non-stroke patients that addressed the cumulative complexity (patients’ demands and capacity) have demonstrated effective interventions for reducing 30-day readmissions, however, the transitional care models for stroke patients have not been well established. Condon and colleagues developed a model of Transitional Stroke Clinic (TSC) led by nurse practitioner(NP) and investigated its role in reducing readmissions by conducting an observational quality improvement study in a single academic, tertiary referral center.

Two phases of transitional care model were implemented from 10/2012 to 09/2015: 

Over 3 years, among 1421 stroke or TIA patient who were discharged home, 510 patient were enrolled into the transitional care model with a mean age of 65 and median NIHSS of 2. A lower TSC show rate was observed in patients readmitted within 30 days (60.8% vs 76.3% not readmitted; p=0.021); a similar trend was noticed in those readmitted within 90 days (67.5% vs 76.4%; p=0.088).
Multivariate analysis showed the TSC visits independently reduced the 30-day readmission by 48% (OR 0.518, 95% CI 0.272, 0.986; p=0.045), and the reduction was not significant for 90-day readmission. Prior stroke and multiple chronic conditions were associated with both 30-day and 90-day readmission.  Other factors that significantly affected 90-day readmission were prior hospitalization, and male gender.
Interestingly, compared with phase I, the phase II protocol made more follow-up phone calls earlier and were able to see all patient in TSC earlier using a structured clinic visit template (although the details of structured vs not structured were not specified), the rate of TSC visit and readmissions in 30 day and 90 day did not differ significantly in two phases.  This is probably because the readmission mainly occurred in high-risks patients, by focusing on this group of population, phase I protocol was able to effectively reduce the readmission rate. In addition, both phases followed the concept of cumulative complexity and spent significant effort on education, coordinating care with referral to therapy and community services, addressing social needs and handing off the care to the primary care which are also important interventions that enhanced patient care.  The phase I model that requires less time and resources may be preferred in future practices, but further investigations are needed. 
With a few limitations (e.g., not covering the patients who were discharged to rehab or skilled nursing facilities with higher NIHSS and who may be at higher risks of readmission, possibility of underestimation of readmission rate), this study showed promising result that early evaluation in NP-led structured transitional clinic was able to reduce readmission at 30 day by about 50% in stroke patients who were discharged home.  We are very glad that a pragmatic clinical trial based on these results is being implemented in North Carolina and we look forward to the standardized, effective and practical transitional care models for stroke survivors.

Low socioeconomic status across age spectrum associated with higher incidence of stroke in adulthood

Low socioeconomic status is associated with a higher incidence risk of stroke in multiple populations worldwide. Although differences in the prevalence and severity of vascular risk factors likely contribute to this disparity, these risks may also be modified by negative socioeconomically driven influences throughout an individual’s lifespan. Becher et al. sought to investigate this further by conducting a case-control study to investigate the contribution of socioeconomic, genetic, and infectious risk factors during childhood, adolescence, and adulthood with respect to the risk of ischemic stroke in adulthood.
The study was nested in a population-based stroke registry in the city of Ludwigshafen, a city in South-West Germany with about 160,000 inhabitants. Patients of Caucasian race-ethnicity ages 18-80 with first-ever ischemic stroke treated at the only stroke unit within the city were compared to age and sex matched controls who were randomly selected from the general population. Patients with prior stroke, myocardial infarction within the last 90 days, dementia or severe communication barriers were excluded. 

Variables that were studied included anthropometric measures, medical history, smoking status, alcohol intake, diet, physical activity and medications. Socioeconomic measures were separated by age group (childhood, up to age 14; adolescence, age 15-25; adulthood,> age 25). Childhood socioeconomic conditions included parents’ occupation (divided into academic, non-academic white collar, blue collar and unskilled labor) during subjects’ childhood as well as living, familial, material and self-estimated financial conditions. For adolescence, highest school degree and professional education was used.  Last, profession, marital status and periods of unemployment were used as conditions for adulthood. Risk scores were calculated prior to analysis by summing scores according to weights chosen a priori based on previous work. Principal component analysis was also performed, as well as classification into tertiles of the summed scores based on distribution in controls. Odds ratio estimates were determined using both univariate and multivariate analyses, with the latter adjusted for known risk factors for stroke and the other life periods. 

A total of 470 subjects agreed to participate in the study and were compared to 809 controls. For childhood conditions, a higher number of siblings (OR=1.48[1.12-1.96]), lack of an own toilet (OR=1.52[1.12-2.05]), and estimated lower family income (OR=2.9[2.18-3.87]) were independently  associated with stroke in multivariate analysis. Lack of vocational training in adolescence (OR=1.93[1.03-3.63]) was independently associated with stroke.  In adulthood, single, divorced or windowed persons (OR=1.63[1.20-2.22]), greater than 6 months of unemployment (OR=1.52[1.05-2.19]) and unskilled last profession (OR=1.99[1.11-3.60]) were independently associated with stroke. In the fully adjusted model (adjusting for age, sex, medical and lifestyle risk factors, and the other life stages), low socioeconomic conditions during childhood (OR=1.77[1.20-2.60]) and adulthood (OR=1.74[1.16-2.60]) were independently associated with stroke risk. Interestingly, adjustment for medical risk factors attenuated the socioeconomic effect in childhood whereas lifestyle risk factors reduced the effect during adolescence and adulthood. When analyzed by stroke subtype, less favorable childhood socioeconomic conditions were associated with a strong risk of large artery stroke (OR=2.13[1.24-3.67]) that was not found for other etiologies of stroke or life stages. 

This study provides an intriguing insight into the impact of various socioeconomic conditions during each stage of life on stroke risk during adulthood. The relatively large number of patients and variety of factors assessed contribute to the strength of the study, although the lack of knowledge about the precise way that socioeconomic conditions affect health makes confounding factors difficult to assess and control. The attenuation of childhood risk after adjustment for medical factors suggests that factors in childhood may be causally linked to the development of known medical risk factors for stroke later in life, and the attenuation of adult risk after adjustment for lifestyle factors suggests that their effects may be independent of medical risk factors. Further study looking at associations with childhood socioeconomic conditions and medical risk factors for stroke could provide further clarity on this issue. The association of low socioeconomic conditions in childhood with large artery strokes may be related to this relationship, as there are many commonalities between medical risk factors for atherogenesis and stroke. The authors’ hypothesis related to chronic systemic inflammation could be further investigated using high-sensitivity CRP values either in a similarly designed study or, ideally, a longitudinal cohort that would track these values over time.   

The racial and geographical homogeneity of the study population limits its generalizability.  Conducting and reviewing similar studies with racially diverse populations in a variety of locations could be helpful in identifying common factors, as there is likely important variation in diet and environmental exposures between low socioeconomic status groups in different regions worldwide. This study and similar studies will be vital in expanding our understanding of how social conditions contribute to stroke risk.

What the FAST-MAG Study teaches us about EMS Systems of Care for Acute Stroke

Danny R. Rose, Jr., MD 

Sanossian N, Liebeskind DS, Eckstein M, Starkman S, Stratton S, Pratt FD, et al. Routing Ambulances to Designated Centers Increases Access to Stroke Center Care and Enrollment in Prehospital Research. Stroke. 2015

Patients with acute stroke have better outcomes when treated at organized stroke centers. Emergency Medical Services (EMS) providers play a critical role in the stroke care system by identifying patients with suspected stroke and then providing rapid transport to a facility providing an appropriate level of specialty care. Since 2007, this notion has been reflected in the American Stroke Association guidelines, which recommend Emergency Medical Services (EMS) systems preferentially route acute stroke patients to certified stroke centers that have proven their capability to deliver stroke care. Although this was supported by legislation or regulations in states and counties covering 53% of the US population by 2010, few studies have investigated whether these policies increase access to stroke center care. The impact on research associated with having a greater proportion of acute stroke patients treated at stroke centers, many of which actively enroll patients in clinical trials, is unknown.

Although the FAST-MAG study, a phase 3 clinical trial for prehospital initiation of magnesium vs. placebo for suspected acute stroke patients, failed to show a statistically significant benefit, it proved the feasibility of conducting a trial utilizing prehospital EMS protocols in a large metropolitan area spanning multiple provider agencies. What makes this study unique was that it was carried out in Los Angeles County over a period that in which there was a substantial change in the way EMS routed patients due to the implementation of a regional system of stroke care. Sanossian et al. performed an analysis using data from this study to investigate how the implementation of preferential routing for acute stroke patients impacted Emergency Department arrival times, the percentage of patients treated at an acute stroke center, and the numbers of patients enrolled in this prehospital stroke study. 

A total of 1627 subjects were enrolled in Los Angeles County over the course of the study, with 863 (53%) prior to and 764 (47%) after adoption of the countywide EMS routing protocol. In the nearly 5 years prior to EMS routing, only 90/863 (10%) of patients were transported to a designated Primary Stroke Center (PSC). EMS routing increased this proportion dramatically, with 698/764 (91%) of patients enrolled after the protocol implementation (P<0.001). Interestingly, the time from EMS arrival on scene to ED arrival actually decreased slightly after the routing change (34.5 min. vs 33.5, p=0.045). An analysis focused on the years immediately before and after the stroke center diversion policy was implemented showed an equally impressive improvement in the percentage of patients transported to PSCs (17% vs. 88%, P<0.0001), shorter scene to door times (33.6 min. vs 34.5, p=0.221), and a greater mean monthly enrollment into the FAST-MAG study (21.2 vs 17.9 subjects per month)

The analysis illustrates the dramatic effect that a properly implemented policy can have on improving the proportion of suspected acute stroke patients treated at stroke centers without detrimentally affecting transport times, one of the most common concerns regarding these types of changes. As these and similar changes designed to ensure acute stroke patients are preferentially treated at Joint Commission-certified stroke centers are implemented, there will likely be benefits beyond the more efficient conduct of clinical trials.

There, however, are significant limitations to the study that affect its generalizability. As in most major metropolitan areas in the US, Los Angeles County has a large amount of adult ED receiving facilities in a relatively small geographic area, with a total of 69 facilities participating in this study. The proportion of these facilities that obtained PSC certification increased steadily throughout the course of the trial, from 9 at the initiation of the routing policy in 2009 to a total of 29 by the trial end in December 2012. Although this can serve as a useful model for other major metropolitan areas in the US, access to primary stroke centers is more limited in large portions of the country. In these areas, routing suspected stroke patients exclusively to stroke centers could result in important delays in evaluation and treatment. This should not discourage policymakers in rural areas from adopting protocols to ensure acute stroke patients are triaged and transported efficiently. In these relatively underserved areas, collaboration and cooperation between stroke centers and critical access hospitals will likely remain a crucial component of stroke systems of care as medical infrastructure continues to evolve and mature.

On developing multi-national acute stroke care quality measures

Neal S. Parikh, MD   

Norrving B, Bray BD, Asplund K, Heuschmann P, Langhorne P, Rudd AG, et al. Cross-National Key Performance Measures of the Quality of Acute Stroke Care in Western Europe. Stroke. 2015 

In this issue of Stroke, representatives from the European Implementation Score Collaboration describe the process and results of an effort to establish common acute stroke care quality measures.

In order to compare quality measures across nations and regions in Western Europe, the collaborators convened to establish agreed-upon metrics. Physician and patient representatives from multiple Western European nations met to establish two tiers of indicators: Tier I – essential, Tier 2 – desirable. The European Stroke Organization endorsed the final measures.

Table 2 summarizes the 30 performance measures of acute stroke care formulated by this group. There are a number of limitations. The measures include basic patient characteristics, but not patients’ basic vascular risk factors, the omission of which limits the ability to make adjusted comparisons across nations. Additionally, while the measures are grossly in concordance with current evidence, they are non-specific. For example, the duration of cardiac arrhythmia detection and the nature of anti-platelet therapy (mono or dual) are not specified. Finally, the outcome measures are rudimentary: 90 day mortality and modified Rankin Scale. These limitations are anticipated given the variability in resources across nations. The authors also admit that the guidelines cannot keep up with research; for example, provision of endovascular therapy is not included in their quality measures.

Given rapidly mounting evidence regarding high-impact stroke treatment and secondary prevention interventions, it is necessary to document acute stroke management quality measures to ultimately facilitate higher levels of evidence-based stroke care. Efforts such as these are important as quality measures may reveal disparities and thereby inform the decisions of policy-makers and funding organizations. Additionally, these quality measures may serve as a model for other nations.