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Scholarly Works (8 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2013)
Approximately 15% of all ischemic strokes (IS) occur in young adults and adolescents. To date, only limited prior public health and research efforts have specifically addressed stroke in the young. Early diagnosis remains challenging because of the lack of awareness and the relative infrequency of stroke compared with stroke mimics. Moreover, the causes of IS in the young are heterogeneous and can be relatively uncommon, resulting in uncertainties about diagnostic evaluation and cause-specific management. Emerging data have raised public health concerns about the increasing prevalence of traditional vascular risk factors in young individuals, and their potential role in increasing the risk of IS, stroke recurrence, and poststroke mortality. These issues make it important to formulate and enact strategies to increase both awareness and access to resources for young stroke patients, their caregivers and families, and health care professionals. The American Academy of Neurology recently convened an expert panel to develop a consensus document concerning the recognition, evaluation, and management of IS in young adults and adolescents. The report of the consensus panel is presented herein.
    Cover page: Recognition and management of stroke in young adults and adolescents
    • Article
    • Peer Reviewed
    Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, Volume 13, Issue 6 (2012)

    Introduction: We determined if targeted education of emergency physicians (EPs)regarding the treatment of mental illness will improve their comfort level in treatingpsychiatric patients boarding in the emergency department (ED) awaiting admission.

    Methods: We performed a pilot study examining whether an educational interventionwould change an EP’s comfort level in treating psychiatric boarder patients (PBPs). Weidentified a set of psychiatric emergencies that typically require admission or treatmentbeyond the scope of practice of emergency medicine. Diagnoses included majordepression, schizophrenia, schizoaffective disorder, bipolar affective disorder, generalanxiety disorder, suicidal ideation, and criminal behavior. We designed equivalentsurveys to be used before and after an educational intervention. Each survey consistedof 10 scenarios of typical psychiatric patients. EPs were asked to rate their comfort levelsin treating the described patients on a visual analogue scale. We calculated summaryscores for the non intervention survey group (NINT) and intervention survey group (INT)and compared them using Student’s t-test.

    Results: Seventy-nine percent (33/42) of eligible participants completed the preinterventionsurvey (21 attendings, 12 residents) and comprised the NINT group. Fiftyfivepercent (23/42) completed the post-intervention survey (16 attendings, 7 residents)comprising the INT group. A comparison of summary scores between ‘NINT’ and ‘INT’groups showed a highly significant improvement in comfort levels with treating thepatients described in the scenarios (P = 0.003). Improvements were noted on separateanalysis for faculty (P = 0.039) and for residents (P = 0.012). Results of a sensitivityanalysis excluding one highly significant scenario showed decreased, but still importantdifferences between the NINT and INT groups for all participants and for residents, butnot for faculty (all: P = 0.05; faculty: P = 0.25; residents: P = 0.03).

    Conclusion: This pilot study suggests that the comfort level of EPs, when asked to treatPBPs, may be improved with education. We believe our data support further study of thisidea and of whether an improved comfort level will translate to a willingness to treat.[West J Emerg Med. 2012;13(6):453-457]

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    Cover page: Does Targeted Education of Emergency Physicians Improve Their Comfort Level in Treating Psychiatric Patients?Creative Commons 'BY-NC' version 4.0 license
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2014)

    Aims

    Epidemiological studies suggest that sex has a role in the pathogenesis of cardioembolic stroke. Since stroke is a vascular disease, identifying sexually dimorphic gene expression changes in blood leukocytes can inform on sex-specific risk factors, response and outcome biology. We aimed to examine the sexually dimorphic immune response following cardioembolic stroke by studying the differential gene expression in peripheral white blood cells.

    Methods and results

    Blood samples from patients with cardioembolic stroke were obtained at ≤3 hours (prior to treatment), 5 hours and 24 hours (after treatment) after stroke onset (n = 23; 69 samples) and compared with vascular risk factor controls without symptomatic vascular diseases (n = 23, 23 samples) (ANCOVA, false discovery rate p≤0.05, |fold change| ≥1.2). mRNA levels were measured on whole-genome Affymetrix microarrays. There were more up-regulated than down-regulated genes in both sexes, and females had more differentially expressed genes than males following cardioembolic stroke. Female gene expression was associated with cell death and survival, cell-cell signaling and inflammation. Male gene expression was associated with cellular assembly, organization and compromise. Immune response pathways were over represented at ≤3, 5 and 24 h after stroke in female subjects but only at 24 h in males. Neutrophil-specific genes were differentially expressed at 3, 5 and 24 h in females but only at 5 h and 24 h in males.

    Conclusions

    There are sexually dimorphic immune cell expression profiles following cardioembolic stroke. Future studies are needed to confirm the findings using qRT-PCR in an independent cohort, to determine how they relate to risk and outcome, and to compare to other causes of ischemic stroke.
      Cover page: Gene Expression in Peripheral Immune Cells following Cardioembolic Stroke Is Sexually Dimorphic
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2013)

      Objective

      Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood-brain barrier is a central feature of HT pathogenesis, and leukocytes may contribute to this process. We sought to determine whether ischemic strokes that develop HT have differences in RNA expression in blood within 3 hours of stroke onset prior to treatment with thrombolytic therapy.

      Methods

      Stroke patient blood samples were obtained prior to treatment with thrombolysis, and leukocyte RNA was assessed by microarray analysis. Strokes that developed HT (n = 11) were compared to strokes without HT (n = 33) and controls (n = 14). Genes were identified (corrected p < 0.05, fold change ≥|1.2|), and functional analysis was performed. RNA prediction of HT in stroke was evaluated using cross-validation, and in a second stroke cohort (n = 52).

      Results

      Ischemic strokes that developed HT had differential expression of 29 genes in circulating leukocytes prior to treatment with thrombolytic therapy. A panel of 6 genes could predict strokes that later developed HT with 80% sensitivity and 70.2% specificity. Key pathways involved in HT of human stroke are described, including amphiregulin, a growth factor that regulates matrix metalloproteinase-9; a shift in transforming growth factor-β signaling involving SMAD4, INPP5D, and IRAK3; and a disruption of coagulation factors V and VIII.

      Interpretation

      Identified genes correspond to differences in inflammation and coagulation that may predispose to HT in ischemic stroke. Given the adverse impact of HT on stroke outcomes, further evaluation of the identified genes and pathways is warranted to determine their potential as therapeutic targets to reduce HT and as markers of HT risk.
        Cover page: RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2014)

        Background

        The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase (recombinant tissue plasminogen activator) alone for moderate or severe ischaemic strokes. Late reperfusion of tissue that was no longer salvageable could be one explanation, as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome. We sought to validate this association in a preplanned analysis of data from the IMS III trial.

        Methods

        We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion (score on Thrombolysis in Cerebral Infarction scale of grade 2-3) during the endovascular procedure (within 7 h of symptom onset). We used logistic regression to model good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) as a function of the time to reperfusion. We prespecified variables to be considered for adjustment, including age, baseline National Institutes of Health Stroke Scale score, sex, and baseline blood glucose concentration.

        Findings

        Of 240 patients who were otherwise eligible for inclusion in our analysis, 182 (76%) achieved angiographic reperfusion. Mean time from symptom onset to reperfusion (ie, procedure end) was 325 min (SD 52). Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome (unadjusted relative risk for every 30-min delay 0·85 [95% CI 0·77-0·94]; adjusted relative risk 0·88 [0·80-0·98]).

        Interpretation

        Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke. Rapid reperfusion could be crucial for the success of future acute endovascular trials.

        Funding

        US National Institutes of Health and National Institute of Neurological Disorders and Stroke.
          Cover page: Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2017)
          Acute ischemic stroke affects over 800,000 US adults annually, with hundreds of thousands more experiencing a transient ischemic attack. Emergent evaluation, prompt acute treatment, and identification of stroke or TIA (transient ischemic attack) etiology for specific secondary prevention are critical for decreasing further morbidity and mortality of cerebrovascular disease. The Biomarkers of Acute Stroke Etiology (BASE) study is a multicenter observational study to identify serum markers defining the etiology of acute ischemic stroke. Observational trial of patients presenting to the hospital within 24 h of stroke onset. Blood samples are collected at arrival, 24, and 48 h later, and RNA gene expression is utilized to identify stroke etiology marker candidates. The BASE study began January 2014. At the time of writing, there are 22 recruiting sites. Enrollment is ongoing, expected to hit 1000 patients by March 2017. The BASE study could potentially aid in focusing the initial diagnostic evaluation to determine stroke etiology, with more rapidly initiated targeted evaluations and secondary prevention strategies.Clinical Trial Registration Clinicaltrials.gov NCT02014896 https://clinicaltrials.gov/ct2/show/NCT02014896?term=biomarkers+of+acute+stroke+etiology&rank=1.
            Cover page: Biomarkers of Acute Stroke Etiology (BASE) Study Methodology
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2017)
              Cover page: Translational Stroke Research
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2021)
              Domain-specific endpoints are assessments that correspond to the output of individual neural systems and are useful for capturing treatment effects on specific behaviors. By contrast, global endpoints combine several attributes into a single score and are useful for capturing broad treatment effects in a summary way. While global endpoints have become the de facto mechanism required to define benefit in stroke trials, they also have important limitations, some of which might be addressed by simultaneously measuring domain-specific endpoints. Substantial opportunity remains to identify quantifiable patient benefit that would otherwise not be captured by global endpoints. Potential advantages of incorporating domain-specific endpoints in acute stroke trials are discussed, such as increased granularity of measurement, improved understanding of how therapies affect the brain between acute treatment and day 90, and optimized therapeutic translation. Potential disadvantages are also considered, including time and cost of administering domain-specific endpoints, as well as statistical implications. Domain-specific endpoints and global endpoints are not mutually exclusive, and both capture clinical benefits to patients. Incorporating a broader set of outcome assessments in stroke trials, including both global and domain-specific endpoints, is warranted.
                Cover page: The Utility of Domain-Specific End Points in Acute Stroke Trials
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