Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Intracellular domain of the IFNaR2 interferon receptor subunit mediates transcription via Stat2

We recently demonstrated that IFNaR2, a subunit of the interferon receptor, can be proteolytically cleaved in response to interferon-alpha and other activators of protein kinase C. Cleavage occurs at multiple sites, via a mechanism similar to that employed by Notch and the Alzheimer's precursor protein, and releases the intracellular domain (ICD). In this study, we demonstrate that the IFNaR2 ICD, when fused to the yeast Gal4 DNA binding domain (Gal4DBD) selectively modulates transcription of four different promoters under the control of Gal4 upstream activating sequences. We previously showed that Stat2 binds constitutively to the ICD of IFNaR2, in a manner that is independent of tyrosine phosphorylation. Here, we show that lCD transcriptional modulation is dependent upon the carboxyl-terminal transactivation domain of Stat2. Specifically, complementing Stat2 deficient cells with wildtype Stat2 restored the ICD-mediated transcriptional effects while complementation with a mutant form of Stat2 lacking the transcriptional activation domain (TAD) did not. In addition, mutation of the Stat2 binding site on the ICD reduced the transcriptional activity of the Gal4DBD-ICD. Finally, we demonstrate that the activity of jak1, a tyrosine kinase also known to bind to IFNaR2, is required for ICD-mediated transcriptional effects. J. Cell. Physiol. 204: 567-573, 2005. (c) 2005 Wiley-Liss, Inc

Abstract W MP76: Diagnostic Accuracy and Characteristics of Missed Ischemic Strokes in the Emergency Department

Objectives: The failure to recognize an acute stroke in the ED represents a missed opportunity for potential thrombolytic therapy and for prompt treatment for secondary prevention. The aim of this study was to examine the diagnostic accuracy of acute ischemic strokes at a large academic center and to identify common characteristics of these missed strokes. Methods: A retrospective review was performed on a random sample of patients &gt;18 years old with a discharge diagnosis of ischemic stroke in 2013. All acute strokes were confirmed on CT or MRI. A stroke was “missed” if practitioners in the ED did not initially consider stroke in the differential, or the diagnosis was delayed causing the patient to miss the therapeutic window for thrombolytic therapy. Results: Two hundred ischemic stroke patients were included in the study. The mean patient age was 72 years, and the mean initial NIHSS was 7. There were 36 “missed” strokes (18%) in this population. Of the strokes that were initially misdiagnosed, 20 of 36 (56%) presented in the time window for thrombolytic therapy and potentially could have received intervention. Posterior circulation strokes were more likely to be missed overall (20/58 posterior, 34%, vs 16/142 anterior, 11%, p &lt; 0.001). Seventy-six percent of patients with posterior stroke had stroke in the original differential compared with 96% in those with anterior circulation stroke (p &lt; 0.001). Symptoms independently associated with posterior circulation strokes included nausea/vomiting (OR=6.9, 95% CI: 2.0-23), headache (OR=6.4, 95% CI: 1.5-27) and difficulty walking (OR=3.5, 95% CI: 1.3-9.5). Anterior circulation patients more commonly presented with focal weakness (OR=0.11, 95% CI: 0.05-0.25) and aphasia (OR=0.17, 95% CI: 0.06-0.45). Conclusions: Despite having a certified stroke program in a large academic medical center, 18% of acute ischemic strokes were missed in the ED. Posterior circulation strokes were 3 times more likely than anterior strokes to be missed. Posterior stroke patients were more likely to present with nausea/vomiting, headache and difficulty walking, and these symptoms should serve as triggers to consider ischemic stroke in the ED. </jats:p

Missed Ischemic Stroke Diagnosis in the Emergency Department by Emergency Medicine and Neurology Services

Background and Purpose— The failure to recognize an ischemic stroke in the emergency department is a missed opportunity for acute interventions and for prompt treatment with secondary prevention therapy. Our study examined the diagnosis of acute ischemic stroke in the emergency department of an academic teaching hospital and a large community hospital. Methods— A retrospective chart review was performed from February 2013 to February 2014. Results— A total of 465 patients with ischemic stroke were included in the analysis; 280 patients from the academic hospital and 185 patients from the community hospital. One hundred three strokes were initially misdiagnosed that is 22% of the included strokes at the combined centers. Fifty-five of these were missed at the academic hospital (20%) and 48 were at the community hospital (26%, P =0.11). Thirty-three percent of missed cases presented within a 3-hour time window for recombinant tissue-type plasminogen activator eligibility. An additional 11% presented between 3 and 6 hours of symptom onset for endovascular consideration. Symptoms independently associated with greater odds of a missed stroke diagnosis were nausea/vomiting (odds ratio, 4.02; 95% confidence interval, 1.60–10.1), dizziness (odds ratio, 1.99; 95% confidence interval, 1.03–3.84), and a positive stroke history (odds ratio, 2.40; 95% confidence interval, 1.30–4.42). Thirty-seven percent of posterior strokes were initially misdiagnosed compared with 16% of anterior strokes ( P &lt;0.001). Conclusions— Atypical symptoms associated with posterior circulation strokes lead to misdiagnoses. This was true at both an academic center and a large community hospital. Future studies need to focus on the evaluation of identification systems and tools in the emergency department to improve the accuracy of stroke diagnosis. </jats:sec

Abstract TP240: Missed Ischemic Stroke Diagnosis in the Emergency Department at an Academic Center and Community Hospital

Introduction: The failure to recognize an ischemic stroke in the emergency department (ED) is a missed opportunity for acute interventions and for prompt treatment with secondary prevention therapy. Our study examined the characteristics of misdiagnosed strokes in the ED of an academic teaching hospital and a large community hospital. Methods: A retrospective chart review was performed from February 2013 to February 2014. A stroke was “missed” if practitioners in the ED did not initially consider stroke in the differential, or the diagnosis was delayed causing the patient to miss the therapeutic window for thrombolytic therapy. Results: A total of 465 ischemic stroke patients were included; 280 patients from the academic hospital and 185 patients from the community hospital. One hundred three strokes were initially misdiagnosed. Fifty-five of these were missed at the academic hospital (22%) and 48 were at the community hospital (26%, p=0.11). Of the missed stroke patients, 26 at the academic hospital (47%) and 10 at the community hospital (21%) presented within 3 hours of symptom onset. At the academic hospital where a neurologist is consulted on all potential acute strokes, a neurologist was called for 95% of the accurate stroke diagnoses but only 36% of the stroke misses (p&lt;0.001). Factors independently associated with greater odds of a missed stroke diagnosis were nausea/vomiting (OR=4.02, 95% CI=1.60-10.1), dizziness (OR=1.99, 95% CI=1.03-3.84), and a positive stroke history (OR=2.40, 95% CI=1.30-4.42). Thirty-seven percent of posterior strokes were initially misdiagnosed compared with 16% of anterior strokes (p&lt;0.001). Conclusion: Greater than 20 percent of stroke patients admitted through the ED at both an academic center and community hospital had a missed diagnosis. These strokes were more likely to be posterior circulation strokes and associated with nausea, vomiting and dizziness. A neurologist consultation decreased the likelihood of a missed stroke. Next steps are the development of improved identification systems and tools in the ED to improve the accuracy of stroke diagnosis. </jats:p

Abstract WMP71: Multimodal Imaging Yields Low Number of Stroke Mimics Treated With Thrombolytic Therapy Without Sacrificing Door-to-Needle Times

Introduction: Speed is critical in fibrinolytic therapy for acute ischemic stroke (AIS), but rapid decision-making may increase tPA use in stroke mimics. Complications from lytics in mimic patients, though uncommon, can be severe. Mimic treatment rates when using non-contrast CT as the only initial imaging modality have increased to as high as 34% with intensified efforts to reduce door to needle (DTN) times. Efficient imaging with MRI or multimodal CT may potentially avoid high mimic treatment rates without prolonging treatment. Methods: In a prospectively maintained registry, we examined all patients treated with IV tPA from January 2010 to June 2015. Institutional policy was to perform MRI first in AIS patients and start tPA on the MR table after DWI showed ischemia and GRE excluded hemorrhage; if MRI could not be performed, multimodal CT with CTA and CTP was performed. Results: Among 319 IV tPA treated patients, age was 71 (±15), 50% were female, and NIHSS was 13.3 (±8.0). Imaging modality before tPA was MR in 193 (61%) and CT in 126 (39%). In the entire population, the DTN time was 54 (IRQ 42-73) mins and the proportion of mimic patients was 3.1%. DTN times decreased steadily throughout the 5.5 year study period, and did not differ among patients imaged with MR vs CT (Figure). The reduction in DTN times was not associated with an increase in mimic-treated rates (Figure). Among the mimic patients, final diagnoses were migraine - 4, seizure - 3, meningitis - 1, PE - 1, and cardiac dysrhythmia - 1. Imaging modalities in mimic patients were MRI in 5 and CT in 5. Preliminary imaging reads suggested abnormality in 2/10, but final reads were normal in all. In 3/10 mimic patients, tPA infusions were stopped before full dose when ongoing imaging further clarified diagnosis. Conclusion: A rapid stroke assessment protocol using MRI or multimodal CT permits swift start of thrombolytic therapy and low rates of stroke mimic treatment. Figure. Door-to-needle time and percent stroke mimics by year. </jats:p