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Purpose: Glaucoma medications reduce the risk of progressive visual field loss, but adherence to these medications is often poor. A better understanding of the appropriate metrics for quantifying glaucoma medication adherence is needed. We describe and compare different means of quantifying glaucoma medication adherence., Methods: Adults with glaucoma were enrolled in a prospective 2-site study. Participants completed a self-report instrument and received electronic medication monitors to use for ∼3 months. Pharmacy records were queried regarding requested refills over the monitoring period; medication possession ratio (MPR) was calculated., Results: Of the 137 total participants, those who answered "Very confident" to the question, "How confident are you that you always remember to use your glaucoma medications?" and "No" to the question, "In the past 4 weeks, did you ever forget to take your medicine?" were more likely [odds ratio (OR) 2.78, 95% confidence interval (CI) 1.19-6.52] to take ≥80% of the prescribed doses according to electronic medication monitors. Mean MPR was 1.49, standard deviation (SD) 0.82, range 0.1-5.31. The proportion of participants taking greater than or equal to 80% of the prescribed doses according to the electronic monitors was 59% for participants with MPR <1.2 (n = 27), 63% for participants with MPR 1.2-1.8 (n = 27), and 88% for MPR >1.8 (n = 25)., Conclusions: Asking about confidence may be a good method of screening for poor adherence for glaucoma medication. MPR may be an inadequate representation of glaucoma medication adherence.

Background and Purpose: Carotid artery atherosclerotic plaque composition may influence plaque stability and risk of thromboembolic events, and noninvasive plaque imaging may therefore permit risk stratification for clinical management. Plaque composition was compared using noninvasive in vivo (3T) and ex vivo (7T) MRI and histopathological examination., Methods: Thirty-three endarterectomy cross-sections, from 13 patients, were studied. The data sets consisted of in vivo 3T MRI, ex vivo 7T MRI, and histopathology. Semiautomated segmentation methods were used to measure areas of different plaque components. Bland-Altman plots and mean difference with 95% confidence interval were carried out., Results: There was general quantitative agreement between areas derived from semiautomated segmentation of MRI data and histology measurements. The mean differences and 95% confidence bounds in the relative to total plaque area between 3T versus Histology were: fibrous tissue 4.99%(-4.56 to 14.56), lipid-rich/necrotic core (LR/NC) with hemorrhage -1.81%(-14.11 to 10.48), LR/NC without hemorrhage -2.43%(-13.04 to 8.17), and calcification -3.18%(-11.55 to 5.18). The mean differences and 95% confidence bounds in the relative to total plaque area between 7T and histology were: fibrous tissue 3.17%(-3.17 to 9.52), LR/NC with hemorrhage -0.55%(-9.06 to 7.95), LR/NC without hemorrhage -12.62%(-19.8 to -5.45), and calcification -2.43%(-9.97 to 4.73)., Conclusions: This study provides evidence that semiautomated segmentation of 3T/7T MRI techniques can help to determine atherosclerotic plaque composition. In particular, the high resolution of ex vivo 7T data was able to highlight greater detail in the atherosclerotic plaque composition. High-field MRI may therefore have advantages for in vivo carotid plaque MRI., (Copyright © 2016 by the American Society of Neuroimaging.)

Background and Purpose: Both intracerebral hemorrhage (ICH) and brain edema have been attributed to reperfusion after intravenous thrombolysis. We explored the interaction of recanalization and core size for imaging outcomes (ICH and vasogenic brain edema)., Methods: In patients with anterior circulation occlusion given intravenous thrombolysis <4.5 hours and imaged with computed tomographic (CT) perfusion and CT angiography, we defined volumes of core (relative delay time >2 s and relative cerebral blood flow <40%) and penumbra (relative delay time >2 s). CT and CT angiography at 24 hours were reviewed for ICH (European Cooperative Acute Stroke Study [ECASS]-2 definition), early vasogenic edema (third International Stroke Trial [IST-3] criteria), and recanalization (thrombolysis in myocardial infarction 2-3). Independent effects of recanalization, core volume and potential interactions on edema, ICH and day 90 outcomes were estimated by logistic regression., Results: In 123 patients, there was a trend for recanalization to be associated with H1/2 ICH (odds ratio [OR], 2.3 [0.97-5.5]; P=0.06) but not with PH1/2 ICH (OR, 1.7 [0.33-8.8]; P=0.5), any edema, or significant brain edema (OR, 1.45 [0.4-4.9]; P=0.55). Ischemic core (>50 mL) was associated with any ICH (OR, 4.0 [1.6-9.5]; P=0.003), edema (OR, 5.4 [2-14]; P<0.01), and significant brain edema (OR, 17.4 [5.3-57]; P<0.01) but not with PH1/2 ICH (OR, 1.2 [0.23-6.5]; P=0.8), after controlling for recanalization. There was no significant interaction of recanalization and large core for any adverse outcomes., Conclusions: Large ischemic core was associated with poorer outcomes and both early vasogenic brain edema and ICH, but recanalization on 24-hour CT angiography was associated with clinically favorable outcome. There was no significant interaction of recanalization and large core volume for any outcomes. The association of hemorrhage or brain edema with post-thrombolysis reperfusion is unclear., (© 2016 American Heart Association, Inc.)

Purpose: A centralized eye donation registry for research could help to bridge the gap between patients interested in donating their eyes to science and scientists who conduct research on human eye tissue. Previous research has demonstrated patient and family support for such a registry. In this study, we assessed the views that eye care professionals have toward an eye donation registry for research., Materials and Methods: Surveys were distributed to all 46 clinical faculty members of the Duke University Eye Center. In addition to collecting demographic information, the surveys assessed clinicians' experience with discussing eye donation with patients, described the proposed eye donation registry for research and asked how the registry would affect the clinicians' practice., Results: A total of 21 eye care professionals returned the survey. Thirty-three percent reported discussing eye donation with patients, and 43% reported that a patient has asked about donating their eyes for research on their disease. Eighty-six percent of eye care professionals reported that a centralized registry would improve the way they work with patients who express a desire to donate their eyes for research., Conclusions: The majority of eye care professionals at our academic institution indicated that an eye donation registry for research would improve how they work with patients who are interested in donating their eyes for research on their disease. Future research should examine how best to communicate this registry to ophthalmic patients.

Respiratory challenge MRI is the modification of arterial oxygen (PaO2) and/or carbon dioxide (PaCO2) concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques.

Background and Purpose: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials., Methods: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials., Results: The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials., Conclusions: Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials., (© 2016 American Heart Association, Inc.)

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak -48, -18, -14; ZE = 5.65, pFWE corr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = -0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population., (© The Author(s) 2016.)

Objectives: The objective of this study was to examine the extent to which patient characteristics, eye drop technique self-efficacy, and ophthalmologist-patient communication about eye drop administration are associated with glaucoma patients' ability to instil a single drop, have the drop land in the eye, and avoid touching the applicator tip of the medication bottle to the eye or face while self-administering eye drops., Methods: Glaucoma patients (n = 279) were recruited from six ophthalmology clinics. Medical visits were videotape-recorded. Afterwards, patients were interviewed and demonstrated administering an eye drop on a videotaped-recording. Generalized estimating equations were used to analyse the data., Key Findings: Ophthalmologists provided eye drop administration instruction to 40 patients. Patients with more years of education were significantly more likely to both instil a single drop (P = 0.017) and have the drop land in their eye (P = 0.017). Women were significantly more likely to touch the applicator tip to their eyes or face (P = 0.014). Patients with severe glaucoma (P = 0.016), women (P = 0.026), and patients who asked at least one eye drop administration question (P = 0.001) were significantly less likely to instil a single drop. Patients with arthritis were significantly less likely to have the drop land in their eye (P = 0.008). African American patients were significantly less likely to touch the applicator tip to their eyes or face (P = 0.008)., Conclusions: Some glaucoma patients have a difficult time self-administering eye drops. As so few patients received eye drop administration instruction from their providers, there is an opportunity for pharmacists to complement care., (© 2015 Royal Pharmaceutical Society.)

Background: The steep, time-dependent loss of benefit from reperfusion in clinical trials is consistent with loss of penumbra over the early hours of ischemia, as observed in animal models. Human imaging studies, however, show persistent penumbra for up to 48 h. We investigated core and penumbra volumes and collateral status in relation to time after stroke onset within the first 6 h., Methods: Using data from three multimodal computer tomography-based studies in acute ischemic stroke patients <6 h after onset, we measured core and penumbra volumes, collateral status, and target mismatch (defined as core volume < 50 ml, perfusion lesion volume > 15 ml, mismatch ratio > 1.8). Patients were grouped by onset to imaging time (<3, 3-4.5, 4.5-6 h). We explored correlates of penumbra proportion by multivariable linear regression., Results: Analysis included 144 subjects. Across time epochs, neither proportions of penumbra (59%, 64%, 75% at <3, 3-4.5, >4. 5 h, respectively, p = 0.4) nor poor collaterals (15/56 (27%), 14/47 (30%), 4/15 (27%) at <3, 3-4.5, >4.5 h, p = 0.9) differed significantly. Penumbra proportion was not clearly related to time to imaging (R(2) = 0.003; p = 0.5) but a trend for divergent effects by collateral status was seen (slight increase in penumbra over time with good collaterals versus reduced with poor, interaction = 0.08). The proportion of patients with target mismatch did not vary by time (56%, 74%, and 67% at <3, 3-4.5, >4.5 h, p = 0.09)., Conclusions: In a cross-sectional sample imaged within 6 h, neither the proportions of penumbral tissue nor "target mismatch" varied by time from onset. A trend for reducing penumbra proportion only among those with poor collaterals may have pathophysiological and therapeutic importance., (© 2016 World Stroke Organization.)

Sister chromatid cohesion is a fundamental prerequisite to faithful genome segregation. Cohesion is precisely regulated by accessory factors that modulate the stability with which the cohesin complex embraces chromosomes. One of these factors, Pds5, engages cohesin through Scc1 and is both a facilitator of cohesion, and, conversely also mediates the release of cohesin from chromatin. We present here the crystal structure of a complex between budding yeast Pds5 and Scc1, thus elucidating the molecular basis of Pds5 function. Pds5 forms an elongated HEAT repeat that binds to Scc1 via a conserved surface patch. We demonstrate that the integrity of the Pds5-Scc1 interface is indispensable for the recruitment of Pds5 to cohesin, and that its abrogation results in loss of sister chromatid cohesion and cell viability., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline., (© The Author(s) 2015.)

Background and Purpose: We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage., Methods: Venous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences., Results: Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase., Conclusions: In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926., (© 2015 American Heart Association, Inc.)

As they grow older, most children with glaucoma must eventually face the transition to self-administering medications. We previously reported factors associated with better or worse medication adherence in children with glaucoma, using an objective, electronic monitor. Utilizing the same data set, the purpose of the current study was to determine whose report (the caregiver's or the child's) corresponded better with electronically monitored adherence. Of the 46 participants (22 girls), the mean age of children primarily responsible, and caregiver primarily responsible for medication administration was 15±2 and 10±2 years, respectively. For the children whose caregiver regularly administered the eyedrops, the caregiver's assessment of drop adherence was associated with measured adherence (P=0.012), but the child's was not (P=0.476). For the children who self-administered eyedrops, neither the child's (P=0.218) nor the caregiver's (P=0.395) assessment was associated with measured percent adherence. This study highlights potential errors when relying on self-reporting of compliance in patients and caregivers with pediatric glaucoma, particularly when the child is responsible for administering their own eyedrops. Frank discussions about the importance of medication adherence and how to improve compliance may help both the child and caregiver better communicate with the treating provider.

Introduction: Adherence to glaucoma medications is essential for successful treatment of the disease but is complex and difficult for many of our patients. Health coaching has been used successfully in the treatment of other chronic diseases. This pilot study explores the use of health coaching for glaucoma care., Methods: A mixed methods study design was used to assess the health coaching intervention for glaucoma patients. The health coaching intervention consisted of four to six health coaching sessions with a certified health coach via telephone. Quantitative measures included demographic and health information, adherence to glaucoma medications (using the visual analog adherence scale and medication event monitoring system), and an exit survey rating the experience. Qualitative measures included a precoaching health questionnaire, notes made by the coach during the intervention, and an exit interview with the subjects at the end of the study., Results: Four glaucoma patients participated in the study; all derived benefits from the health coaching. Study subjects demonstrated increased glaucoma drop adherence in response to the coaching intervention, in both visual analog scale and medication event monitoring system. Study subjects' qualitative feedback reflected a perceived improvement in both eye and general health self-care. The subjects stated that they would recommend health coaching to friends or family members., Conclusion: Health coaching was helpful to the glaucoma patients in this study; it has the potential to improve glaucoma care and overall health.

Little is known about how ophthalmologist-patient communication over time is associated with glaucoma patient long-term adherence. The purpose of our study was to examine the association between provider use of components of the resources and supports in self-management model when communicating with patients and adherence to glaucoma medications measured electronically over an 8-month period. In this longitudinal prospective cohort study, the main variables studied were ophthalmologist communication-individualized assessment, collaborative goal setting and skills enhancement. Patients with glaucoma who were newly prescribed or on glaucoma medications were recruited from six ophthalmology clinics. Patients' baseline and next follow-up visits were videotape-recorded. Patients were interviewed after their visits. Patients used medication event monitoring systems (MEMS) for 8 months after enrollment into the study, and adherence was measured electronically using MEMS for 240 days after their visits. Two hundred and seventy-nine patients participated. Patient race and regimen complexity were negatively associated with glaucoma medication adherence over an 8-month period. Provider communication behaviors, including providing education and positive reinforcement, can improve patient adherence to glaucoma medications over an 8-month period., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rationale: Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator., Aims and Design: This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group., Study Outcomes: This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow., Discussion: This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication., (© 2015 World Stroke Organization.)

Objective: The goal of the study was to determine which glaucoma quiz provides the best information about patient glaucoma knowledge to clinicians in clinical practice settings., Methods: Four glaucoma quizzes were identified from the literature and national eye education programs and were qualitatively analyzed to categorize questions by topic. Quizzes were assessed by 64 glaucoma specialists using an online survey, with descriptive statistics. Comments about the quizzes were analyzed qualitatively using themes and representative quotations., Results: Quizzes covered content that was important for glaucoma diagnosis and management. The National Eye Health Education Program (NEHEP) and Prevent Blindness America quizzes covered primarily diagnosis, screening, and risk factors, and the quizzes from the literature primarily covered causes of glaucoma, vision loss, eye drops, and systemic disease. Overall, the NEHEP quiz was ranked best for clinical practice, ranked first by 38%. Ranked second overall, the Gray quiz was ranked first by 34% and last by 34%., Conclusion: The NEHEP quiz was rated most useful for assessing baseline general glaucoma knowledge for a busy clinical practice. The Gray quiz appears to be more useful as part of a comprehensive education program, perhaps in combination with an ophthalmic educator.

Background: Glaucoma is an important cause of irreversible blindness. This study describes the characteristics of a large, diverse group of glaucoma patients and evaluates associations between demographic and clinical characteristics and blindness., Methods: Data were gathered via retrospective chart review of patients (N = 1,454) who were seen between July 2007 and July 2010 by glaucoma service providers at Duke Eye Center. Visual acuity and visual field criteria were used to determine whether patients met the criteria for legal blindness. Descriptive and comparative statistical analyses were performed on the glaucoma patients who were not blind (n = 1,258) and those who were blind (n = 196). A subgroup analysis of only those patients with primary open-angle glaucoma was also performed., Results: In this tertiary care population, 13% (n = 196) of glaucoma patients met criteria for legal blindness, nearly one-half of whom (n = 94) were blind from glaucoma, and another one-third of whom (n = 69) had glaucoma-related blindness. The most common glaucoma diagnosis at all levels of vision was primary open-angle glaucoma. A larger proportion of black patients compared with white patients demonstrated vision loss; the odds ratio (OR) for blindness was 2.25 (95% CI, 1.6-3.2) for black patients compared with white patients. The use of systemic antihypertensive medications was higher among patients who were blind compared with patients who were not blind (OR = 2.1; 95% CI, 1.4-3.1). A subgroup analysis including only patients with primary open-angle glaucoma showed similar results for both black race and use of systemic antihypertensive medications. The relationship between use of systemic antihypertensive medications and blindness was not different between black patients and white patients (interaction P = .268)., Limitations: Data were based on chart review, and associations may be confounded by unmeasured factors., Conclusions: Treated systemic hypertension may be correlated with blindness, and the cause cannot be explained solely by race. In addition, this study demonstrated that there is continued disparity between black patients and white patients with regards to blindness from glaucoma., (©2015 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Purpose: Glaucoma medications can improve clinical outcomes when patients adhere to their medication regimen. Providers often ask patients with glaucoma to self-report their adherence, but the accuracy of self-reporting has received little scientific attention. The purpose of this article was to compare a self-reported medication adherence measure with adherence data collected from Medication Event Monitoring Systems (MEMS) electronic monitors. An additional goal was to identify which patient characteristics were associated with overreporting adherence on the self-reported measure., Methods: English-speaking adult patients with glaucoma were recruited from 6 ophthalmology practices for this observational cohort study. Patients were interviewed after their initial visit and were given MEMS contains, which recorded adherence over a 60-day period. MEMS percent adherence measured the percentage of the prescribed number of doses taken. MEMS-measured timing adherence assessed the percent doses taken on time. Patients self-reported adherence to their glaucoma medications on a visual analog scale (VAS) ~60 days after the baseline visit. Bivariate analyses and logistic regressions were used to analyze the data. Self-reported medication adherence on the VAS was plotted against MEMS adherence to illustrate the discrepancy between self-reported and electronically monitored adherence., Findings: The analyses included 240 patients who returned their MEMS containers and self-reported medication adherence at the 60-day follow-up visit. Compared with MEMS-measured percent adherence, 31% of patients (n = 75) overestimated their adherence on the VAS. Compared with MEMS-measured timing adherence, 74% (n = 177) of patients overestimated their adherence. For the MEMS-measured percent adherence, logistic regression revealed that patients who were newly prescribed glaucoma medications were significantly more likely to overreport adherence on the VAS (odds ratio, 3.07 [95% CI, 1.22-7.75]). For the MEMS-measured timing adherence, being male (χ(2) test, 6.78; P = 0.009) and being prescribed glaucoma medications dosed multiple times daily (χ(2) test, 4.02; P = 0.045) were significantly associated with patients overreporting adherence. However, only male sex remained a significant predictor of overreporting adherence in the logistic regression (odds ratio, 4.05 [95% CI, 1.73-9.47])., Implications: Many patients with glaucoma, especially those newly diagnosed, overestimated their medication adherence. Because patients were likely to overreport the percent doses taken and timing adherence, providers may want to ask patients additional questions about when they take their glaucoma medications to potentially detect issues with taking these medications on time., (Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.)

Objective: We examined whether six patient-provider communication behaviors directly affected the intraocular pressure (IOP) of glaucoma patients or whether patient medication adherence and eye drop technique mediated the relationship between self-efficacy, communication, and IOP., Methods: During an 8-month, longitudinal study of 279 glaucoma patients and 15 providers, two office visits were videotape-recorded, transcribed, and coded for six patient-provider communication behaviors. Medication adherence was measured electronically and IOP was extracted from medical records. We ran generalized estimating equations to examine the direct effects of communication on IOP and used bootstrapping to test whether medication adherence and eye drop technique mediated the effect of communication on IOP., Results: Provider education about medication adherence (B=-0.50, p<0.05) and inclusion of patient input into the treatment plan (B=-0.35, p<0.05) predicted improved IOP. There was no evidence of significant mediation., Conclusion: The positive effects of provider education and provider inclusion of patient input in the treatment plan were not mediated by adherence and eye drop technique., Practice Implications: Providers should educate glaucoma patients about the importance of medication adherence and include patient input into their treatment plan., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of this study was to examine if patient demographic factors influenced self-reporting of medication side effects, difficulty with drop instillation, and nonadherence to glaucoma therapy., Methods: English-speaking adult glaucoma patients (n = 279) from six ophthalmology clinics were enrolled. Patients' medical visits were videotaped and patients were interviewed immediately afterward by research assistants. The videotapes were transcribed verbatim and coded to identify patients who expressed problems with medication side effects, eye drop administration, and nonadherence during the glaucoma office visits. Generalized estimating equations were performed to identify whether patient characteristics were associated with expression of problems with glaucoma medication and medication nonadherence during the office visit., Results: Patients with lower health literacy were significantly less likely to express problems with side effects (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.25 to 0.88) and eye drop administration (OR, 0.26; 95% CI, 0.11 to 0.63) during the visit. Patients who reported eye drop administration and side effect problems during the interview were significantly more likely to express these problems to their ophthalmologist (OR, 3.13; 95% CI, 1.82 to 5.37 and OR, 1.86; 95% CI, 1.12 to 3.08, respectively). Patients who expressed a problem with eye drop administration and with side effects were significantly more likely to express medication nonadherence to their ophthalmologist (OR, 2.89; 95% CI, 1.44 to 5.80 and OR, 2.03; 95% CI, 1.16 to 3.54, respectively). Patients who reported greater than 80% medication adherence during the interview were significantly less likely to express nonadherence to their ophthalmologist (OR, 0.22; 95% CI, 0.12 to 0.40)., Conclusions: Eye care providers should be aware that glaucoma patients with lower health literacy are less likely to express problems with side effects and eye drop administration. Providers should work with patients to assess medication-related problems to mitigate potential barriers to medication adherence because patients who expressed medication problems were also more likely to express nonadherence.

Objective: To examine the associations of provider-patient communication, glaucoma medication adherence self-efficacy, and outcome expectations with glaucoma medication adherence., Design: Prospective, observational cohort study., Participants: Two hundred seventy-nine patients with glaucoma who were newly prescribed or taking glaucoma medications were recruited at 6 ophthalmology clinics., Methods: Patients' visits were video recorded and communication variables were coded using a detailed coding tool developed by the authors. Adherence was measured using Medication Event Monitoring Systems for 60 days after their visits., Main Outcome Measures: The following adherence variables were measured for the 60-day period after their visits: whether the patient took 80% or more of the prescribed doses, percentage of the correct number of prescribed doses taken each day, and percentage of the prescribed doses taken on time., Results: Higher glaucoma medication adherence self-efficacy was associated positively with better adherence with all 3 measures. Black race was associated negatively with percentage of the correct number of doses taken each day (β = -0.16; P < 0.05) and whether the patient took 80% or more of the prescribed doses (odds ratio, 0.37; 95% confidence interval, 0.16-0.86). Physician education about how to administer drops was associated positively with percentage of the correct number of doses taken each day (β = 0.18; P < 0.01) and percentage of the prescribed doses taken on time (β = 0.15; P < 0.05)., Conclusions: These findings indicate that provider education about how to administer glaucoma drops and patient glaucoma medication adherence self-efficacy are associated positively with adherence., Competing Interests: Drs. Sleath, Blalock, Carpenter, Muir, Sayner, Giangiacomo, and Slota indicate no conflict of interest., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Opinion Statement: Intravenous thrombolysis with the recombinant tissue plasminogen activator alteplase is the standard of care for patients with acute ischaemic stroke presenting within 4.5 h of symptom onset. The odds of independent survival decline steeply with longer time to treatment delivery, reflecting progressive ischaemic damage to the brain. Standards accordingly emphasise optimisation of patient pathways to minimise treatment delays. Observational data and international clinical guidelines support the safety and efficacy of alteplase in many patient groups currently excluded from treatment (e.g. seizure at onset, concomitant diabetes and previous stroke) on the basis of historical clinical trial criteria. Future evolution of thrombolysis will optimise dosing, apply advanced imaging to extend treatment to groups currently excluded and investigate novel drugs, and adjunctive drug and device therapies. To date, trials of novel therapeutic approaches that have been applied at later time points have failed to demonstrate benefit, suggesting that the future gains are likely to arise from applications within current time windows.

Background: In most countries, alteplase given within 4·5 h of onset is the only approved medical treatment for acute ischaemic stroke. The newer thrombolytic drug tenecteplase has been investigated in one randomised trial up to 3 h after stroke and in another trial up to 6 h after stroke in patients selected by advanced neuroimaging. In the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST), we aimed to assess the efficacy and safety of tenecteplase versus alteplase within 4·5 h of stroke onset in a population not selected on the basis of advanced neuroimaging, and to use imaging biomarkers to inform the design of a definitive phase 3 clinical trial., Methods: In this single-centre, phase 2, prospective, randomised, open-label, blinded end-point evaluation study, adults with supratentorial ischaemic stroke eligible for intravenous thrombolysis within 4·5 h of onset were recruited from The Institute of Neurological Sciences, Glasgow, Scotland. Patients were randomly assigned (1:1) to receive tenecteplase 0·25 mg/kg (maximum 25 mg) or alteplase 0·9 mg/kg (maximum 90 mg). Treatment allocation used a mixed randomisation and minimisation algorithm including age and National Institutes of Health Stroke Scale score, generated by an independent statistician. Patients were not informed of treatment allocation; treating clinicians were aware of allocation but those assessing the primary outcome were not. Imaging comprised baseline CT, CT perfusion, and CT angiography; and CT plus CT angiography at 24-48 h. The primary endpoint was percentage of penumbra salvaged (CT perfusion-defined penumbra volume at baseline minus CT infarct volume at 24-48 h). Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT01472926., Findings: Between Jan 1, 2012, and Sept 7, 2013, 355 patients were screened, of whom 157 were eligible for intravenous thrombolysis, and 104 patients were enrolled. 52 were assigned to the alteplase group and 52 to tenecteplase. Of 71 patients (35 assigned tenecteplase and 36 assigned alteplase) contributing to the primary endpoint, no significant differences were noted for percentage of penumbral salvaged (68% [SD 28] for the tenecteplase group vs 68% [23] for the alteplase group; mean difference 1·3% [95% CI -9·6 to 12·1]; p=0·81). Neither incidence of symptomatic intracerebral haemorrhage (by SITS-MOST definition, 1/52 [2%] tenecteplase vs 2/51 [4%] alteplase, p=0·55; by ECASS II definition, 3/52 [6%] vs 4/51 [8%], p=0·59) nor total intracerebral haemorrhage events (8/52 [15%] vs 14/51 [29%], p=0·091) differed significantly. The incidence of serious adverse events did not differ between groups (32 in the tenecteplase group, three considered probably or definitely related to drug treatment; 16 in the alteplase group, five were considered drug-related)., Interpretation: Neurological and radiological outcomes did not differ between the tenecteplase and alteplase groups. Evaluation of tenecteplase in larger trials of patients with acute stroke seems warranted., Funding: The Stroke Association., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Purpose: Mutations in NOTCH3 cause cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated., Methods: We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay., Results: We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy sibling. All mutation carriers exhibited a CADASIL typical brain imaging and clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro aggregation behavior of the D80G mutant was similar compared with cysteine-affecting mutations. This was reproduced with cysteine-sparing mutations from previously reported families having a phenotype consistent with CADASIL., Conclusions: Our findings support the view that cysteine-sparing mutations, such as D80G, might cause CADASIL with a phenotype largely indistinguishable from cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3 mutations offers novel insights into pathomechanisms and might represent a tool for estimating their clinical significance., (© 2015 American Heart Association, Inc.)

Background: Acute ischemic stroke is common and disabling, but there remains a paucity of acute treatment options and available treatment (thrombolysis) is underutilized. Advanced brain imaging, designed to identify viable hypoperfused tissue (penumbra), could target treatment to a wider population. Existing magnetic resonance imaging and computed tomography-based technologies are not widely used pending validation in ongoing clinical trials. T2* oxygen challenge magnetic resonance imaging, by providing a more direct readout of tissue viability, has the potential to identify more patients likely to benefit from thrombolysis - irrespective of time from stroke onset - and patients within and beyond the 4·5 h thrombolysis treatment window who are unlikely to benefit and are at an increased risk of hemorrhage., Aims: This study employs serial multimodal imaging and voxel-based analysis to develop optimal data processing for T2* oxygen challenge penumbra assessment. Tissue in the ischemic hemisphere is compartmentalized into penumbra, ischemic core, or normal using T2* oxygen challenge (single threshold) or T2* oxygen challenge plus cerebral blood flow (dual threshold) data. Penumbra defined by perfusion imaging/apparent diffusion coefficient mismatch (dual threshold) is included for comparison., Methods: Permanent middle cerebral artery occlusion was induced in male Sprague-Dawley rats (n = 6) prior to serial multimodal imaging: T2* oxygen challenge, diffusion-weighted and perfusion imaging (cerebral blood flow using arterial spin labeling)., Results: Across the different methods evaluated, T2* oxygen challenge combined with perfusion imaging most closely predicted 24 h infarct volume. Penumbra volume declined from one to four-hours post-stroke: mean ± SD, 77 ± 44 to 49 ± 37 mm(3) (single T2* oxygen challenge-based threshold); 55 ± 41 to 37 ± 12 mm(3) (dual T2* oxygen challenge/cerebral blood flow); 84 ± 64 to 42 ± 18 mm(3) (dual cerebral blood flow/apparent diffusion coefficient), as ischemic core grew: 155 ± 37 to 211 ± 36 mm(3) (single apparent diffusion coefficient threshold); 178 ± 56 to 205 ± 33 mm(3) (dual T2* oxygen challenge/cerebral blood flow); 139 ± 30 to 168 ± 38 mm(3) (dual cerebral blood flow/apparent diffusion coefficient). There was evidence of further lesion growth beyond four-hours (T2-defined edema-corrected infarct, 231 ± 19 mm(3) )., Conclusions: In conclusion, T2* oxygen challenge combined with perfusion imaging has advantages over alternative magnetic resonance imaging techniques for penumbra detection by providing serial assessment of available penumbra based on tissue viability., (© 2014 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.)

We applied the ecologic model of communication in medical consultations to examine how patient, physician, and situational/contextual factors are associated with whether patients ask one or more questions about glaucoma and glaucoma medications during visits to ophthalmologists. Patients with glaucoma who were newly prescribed or already on glaucoma medications were recruited at six ophthalmology clinics. Patients' visits with their doctors were video-recorded and patients were interviewed after visits. Generalized estimating equations were used to analyze the data. Two hundred and seventy-nine patients participated. Patients asked one or more questions about glaucoma during 59% of visits and about glaucoma medications during 48% of visits. Patients who were newly prescribed glaucoma medications were significantly more likely to ask one or more questions about glaucoma and glaucoma medications. Whether providers asked patients if they had questions was not significantly associated with patient question-asking. Patients were significantly more likely to ask older providers questions about glaucoma medications and female providers questions about glaucoma. Eye care providers should encourage glaucoma patients to ask questions during their medical visits.

Background and Purpose: Computed tomography perfusion provides information on tissue viability according to proposed thresholds. We evaluated thresholds for ischemic core and tissue at risk and subsequently tested their accuracy in independent datasets., Materials and Methods: Tissue at risk was evaluated in patients with persistent arterial occlusions, and ischemic core thresholds in patients with recanalization and major clinical improvement. Scans were randomly allocated to derivation or validation groups for tissue at risk and core analysis. Optimum thresholds using mean transit time (MTT), cerebral blood flow (CBF), cerebral blood volume, and delay time (DT) were assessed., Results: Absolute MTT, relative MTT and DT were best derived predictors of tissue at risk with thresholds of ≥ 7 seconds, ≥ 125%, and ≥ 2 seconds respectively. DT ≥ 2 seconds was the best predictor in the validation dataset (95% agreement levels = -44 to +30 mL, Bias = -6.9). Absolute and relative MTT were the best derived predictors of infarct volume in the core group (8 seconds and 125% respectively) but relative CBF of ≤ 45% performed best in the core validation dataset., Conclusions: Time-based perfusion thresholds perform well as predictors of tissue at risk of infarction with DT the best predictor. Relative CBF was the best predictor of ischemic core. Evaluation in larger populations is needed to confirm the performance of tissue viability thresholds., (Copyright © 2014 by the American Society of Neuroimaging.)

Background and Purpose: The σ-1 receptor (Sig-1R) agonist cutamesine (SA4503) enhanced functional recovery after experimental stroke with a treatment initiation window of 48 hours and chronic treatment for 28 days. We conducted a phase 2 clinical trial exploring the safety, tolerability, dose range, and functional effects of cutamesine in patients with ischemic stroke., Methods: Subjects were randomized between 48 and 72 hours after stroke to receive cutamesine 1 mg/d, 3 mg/d, or placebo for 28 days. Effects on safety and function were assessed at baseline, at end of treatment (day 28), and at end of follow-up (day 56)., Results: In 60 patients, treatment with both cutamesine dosages was safe and well tolerated without significant differences in numbers of treatment emergent or serious adverse events. No significant effect was observed on the primary efficacy measure (change in National Institutes of Health Stroke Scale from baseline to day 56) or modified Rankin Scale and Barthel Index scores. Post hoc analysis of moderately and severely affected patients (baseline National Institutes of Health Stroke Scale, ≥7 and ≥10) showed greater National Institutes of Health Stroke Scale improvements in the 3 mg/d cutamesine group when compared with placebo (P=0.034 and P=0.038, respectively). A trend toward a higher proportion being able to complete a 10m timed walk was observed for cutamesine-treated subjects., Conclusions: Cutamesine was safe and well tolerated at both dosage levels. Although no significant effects on functional end points were seen in the population as a whole, greater improvement in National Institutes of Health Stroke Scale scores among patients with greater pretreatment deficits seen in post hoc analysis warrants further investigation. Additional studies should focus on the patient population with moderate-to-severe stroke., Clinical Trial Registration Url: http://www.clinicaltrials.gov/show/NCT00639249. Unique identifier: NCT00639249. The EudraCT number is 2007-004840-60 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004840-60/GB)., (© 2014 American Heart Association, Inc.)

Objectives: CADASIL is a monogenic small vessel vasculopathy causing recurrent stroke. Early descriptions suggested dementia and disability were common from the 5th decade but there is evidence of marked phenotypic variability. We investigated the prevalence and clinical features of CADASIL in the west of Scotland., Methods: We undertook a retrospective review of clinical records of patients with confirmed CADASIL identified through a specialist clinic. Patients were divided to examine the effect of date of diagnosis on clinical outcomes and the characteristics at different ages. The location of pedigree members was used to estimate prevalence., Results: Twenty-one different CADASIL-causing NOTCH3 mutations were identified in 49 pedigrees (61% in exon 4). Disease prevalence in Glasgow was 4.6/100,000 adults. Mutation prevalence was estimated at 10.7/100,000 population. Median age at first stroke in women (57 years) was higher than previous estimates, and stroke age in men was higher in patients diagnosed more recently (pre 2006 46 years, post 2006 56 years, P=0.034). In patients over 58 years of age, 13/34 (38%) were living independently and 17/28 (61%) were mobile without aids when last seen., Conclusions: CADASIL prevalence is at least 4.6 per 100,000 adults. Median age of first stroke may be older than previously thought. Clinicians should consider CADASIL in the differential diagnosis even in older patients with stroke., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale: In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. MRI can identify patients within the time-window for thrombolysis (≤4·5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging., Aims and Hypothesis: The study aims to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo., Design: WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo., Study Outcome: The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4-6 at 90 days., Discussion: If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background: Many factors influence glaucoma medication adherence. A better understanding of the relationships between health literacy, depressive symptoms, and patient-reported problems in using glaucoma medications may reveal opportunities for intervention that could improve patients' clinical outcomes., Objective: To examine the relationship between patient characteristics (demographics, health literacy, and depressive symptoms) and patient-reported problems in using glaucoma medications and to assess factors related to patients' self-reported adherence to glaucoma medications., Methods: Patients diagnosed with primary open-angle glaucoma (n = 228) currently taking intraocular pressure-lowering medications were recruited at 6 ophthalmology clinics. Patients were interviewed to identify problems using glaucoma medications, and self-reported medication adherence was determined using a Visual Analog Scale. Questionnaires were administered to assess health literacy, depressive symptoms, outcome expectations, and medication self-efficacy., Results: Younger patients (P = 0.03), patients with depressive symptoms (P = 0.02), and patients who reported more medication problems (P = 0.005) were significantly less adherent to their glaucoma medications. Patients with higher glaucoma medication self-efficacy adherence scores (P = 0.003) and higher outcome expectations (P = 0.03) were significantly more adherent., Conclusions: Providers should consider using tools to screen glaucoma patients for depressive symptoms and for problems in using medications to identify patients who are at higher risk of nonadherence to treatment and who might benefit from follow-up with primary care providers., (© The Author(s) 2014.)

Objectives: The purpose of this study was to identify risk factors for exposure of glaucoma drainage devices (GDD)., Setting: This retrospective, observational study was conducted in the eye clinic of an academic medical centre., Participants: Participants included 1073 consecutive adults who underwent GDD surgery between 1 January 2005 and 1 January 2011. Participants were included if chart review indicated GDD surgery during the study period and excluded if at least 12 months of clinical follow-up was not available in the medical record., Primary Outcome Measure: The primary outcome measure was exposure of the GDD occurring at least 1 month after implant surgery. The characteristics of participants who experienced exposure of the implant were compared to the characteristics of participants who did not experience exposure., Results: Of the 1073 participants having undergone GDD surgery, 67 experienced exposure of the device. Neither the type of GDD, type of patch graft (eye bank sclera, Tutoplast sclera and Tutoplast pericardium), surgeon, location of GDD, number of GDD previously implanted into the eye, nor history of diabetes or uveitis were associated with likelihood of exposure. Women were more likely than men to experience exposure of the GDD (OR 2.004 (95% CI1.170 to 3.431)) in both univariable (p=0.011) and multivariable (p=0.013) analyses. In survival analysis, exposure of the GDD occurred earlier for women than for men (58 vs 61 months; p=0.024).White race (vs black) was also associated with increased risk of GDD exposure (OR 1.693 (95% CI 1.011 to 2.833)) in univariable (p=0.044) and multivariable (p=0.046) analyses., Conclusions: Women are two times more likely to experience GDD exposure than men, independent of age. White race is also a risk factor for exposure.

Purpose: The purpose of this preliminary study was to describe the extent to which providers used collaborative goal setting and individualized assessment with patients who were newly prescribed glaucoma medications., Methods: English-speaking glaucoma suspect patients from six ophthalmology clinics who were newly prescribed glaucoma medications had their medical visits videotaped and were interviewed after the visits. The videotapes were transcribed and coded to examine provider use of collaborative goal setting and individualized assessment., Results: Fifty-one patients seeing 12 ophthalmologists participated. Providers gave patients glaucoma treatment options during 37% of the visits; only five providers gave patients treatment options Providers asked for patient treatment preferences in less than 20% of the visits; only two providers asked for patient treatment preferences. Providers were significantly more likely to ask African American patients for their preferences or ideas concerning treatment than non-African American patients (Pearson χ² = 4.1, p = 0.04). Providers were also significantly more likely to ask African American patients about their confidence in using glaucoma medication regularly than non-African American patients (Pearson χ² = 8.2, p = 0.004). Providers asked about patient views about glaucoma in less than 20% of the visits; five providers asked patients their views on glaucoma and its treatment. Providers were significantly more likely to ask African American patients about their views on glaucoma than non-African American patients (Pearson χ² = 5.62, p = 0.02)., Conclusions: Eye care providers often did not use collaborative goal setting or conduct individualized assessments of patient views on glaucoma when prescribing treatment for the first time.

Background: The learning preferences of ophthalmology patients were examined., Methods: Results from a voluntary survey of ophthalmology patients were analyzed for education preferences and for correlation with race, age, and ophthalmic topic., Results: To learn about eye disease, patients preferred one-on-one sessions with providers as well as printed materials and websites recommended by providers. Patients currently learning from the provider were older (average age 59 years), and patients learning from the Internet (average age 49 years) and family and friends (average age 51 years) were younger. Patients interested in cataracts, glaucoma, macular degeneration, and dry eye were older; patients interested in double vision and glasses were younger. There were racial differences regarding topic preferences, with Black patients most interested in glaucoma (46%), diabetic retinopathy (31%), and cataracts (28%) and White patients most interested in cataracts (22%), glaucoma (22%), and macular degeneration (19%)., Conclusion: MOST OPHTHALMOLOGY PATIENTS PREFERRED PERSONALIZED EDUCATION: one-on-one with their provider or a health educator and materials (printed and electronic) recommended by their provider. Age-related topics were more popular with older patients, and diseases with racial risk factors were more popular with high risk racial groups.

Stroke affects one in every six people worldwide, and is the leading cause of adult disability. Some spontaneous recovery is usual but of limited extent, and the mechanisms of late recovery are not completely understood. Endogenous neurogenesis in humans is thought to contribute to repair, but its extent is unknown. Exogenous cell therapy is promising as a means of augmenting brain repair, with evidence in animal stroke models of cell migration, survival, and differentiation, enhanced endogenous angiogenesis and neurogenesis, immunomodulation, and the secretion of trophic factors by stem cells from a variety of sources, but the potential mechanisms of action are incompletely understood. In the animal models of stroke, both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) improve functional recovery, and MSCs reduce the infarct volume when administered acutely, but the heterogeneity in the choice of assessment scales, publication bias, and the possible confounding effects of immunosuppressants make the comparison of effects across cell types difficult. The use of adult-derived cells avoids the ethical issues around embryonic cells but may have more restricted differentiation potential. The use of autologous cells avoids rejection risk, but the sources are restricted, and culture expansion may be necessary, delaying treatment. Allogeneic cells offer controlled cell numbers and immediate availability, which may have advantages for acute treatment. Early clinical trials of both NSCs and MSCs are ongoing, and clinical safety data are emerging from limited numbers of selected patients. Ongoing research to identify prognostic imaging markers may help to improve patient selection, and the novel imaging techniques may identify biomarkers of recovery and the mechanism of action for cell therapies.

Although reporting vision-related quality of life (VRQoL) outcomes has become increasingly common in adult glaucoma studies, little is known about the influence of disease severity, medication burden, and surgical experience on the quality of life of children with glaucoma. We tested the feasibility of administering a self-reported VRQoL instrument and describe the VRQoL in children with glaucoma. Better VRQoL was correlated with higher visual acuity in the better-seeing eye but not the number of surgeries the child had undergone or the number of prescribed eyedrops., (Published by Mosby, Inc.)

Objective. The purpose of this study was to examine how patient, physician, and situational factors are associated with the extent to which providers educate patients about glaucoma and glaucoma medications, and which patient and provider characteristics are associated with whether providers educate patients about glaucoma and glaucoma medications. Methods. Patients with glaucoma who were newly prescribed or on glaucoma medications were recruited and a cross-sectional study was conducted at six ophthalmology clinics. Patients' visits were videotape recorded and patients were interviewed after visits. Generalized estimating equations were used to analyze the data. Results. Two hundred and seventy-nine patients participated. Providers were significantly more likely to educate patients about glaucoma and glaucoma medications if they were newly prescribed glaucoma medications. Providers were significantly less likely to educate African American patients about glaucoma. Providers were significantly less likely to educate patients of lower health literacy about glaucoma medications. Conclusion. Eye care providers did not always educate patients about glaucoma or glaucoma medications. Practice Implications. Providers should consider educating more patients about what glaucoma is and how it is treated so that glaucoma patients can better understand their disease. Even if a patient has already been educated once, it is important to reinforce what has been taught before.

Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.

The recently published second Surgical Trial in Intracerebral Haemorrhage (STICH-2) tested whether surgical evacuation of superficial spontaneous intracerebral haemorrhage was effective at reducing death and disability at 6 months after onset. Participants were randomised to a policy of early surgical intervention or initial medical management alone within 48 hours of symptom onset. After enrolling 601 patients across 78 centres in 27 countries, intention to treat analysis showed no difference in outcome. Time to intervention was a median of 26 hours after symptom onset in the surgical arm, and craniotomy accounted for 98% of all surgical procedures. The interpretation of the overall neutral result is confounded by a high proportion of crossovers from the medical management arm of the study, predominantly of more severely affected patients. Further analysis may clarify whether decompressive surgery late after superficial intracerebral haemorrhage has any role in management., (© 2013 The Author. International Journal of Stroke © 2013 World Stroke Organization.)

Background: In randomised trials testing treatments for acute ischaemic stroke, imaging markers of tissue reperfusion and arterial recanalisation may provide early response indicators., Objective: To determine the predictive value of structural, perfusion and angiographic imaging for early and late clinical outcomes and assess practicalities in three comprehensive stroke centres., Methods: We recruited patients with potentially disabling stroke in three stroke centres, performed magnetic resonance (MR) or CT, including perfusion and angiography imaging, within 6 h, at 72 h and 1 month after stroke. We assessed the National Institutes of Health Stroke Scale (NIHSS) score serially and functional outcome at 3 months, tested associations between clinical variables and structural imaging, several perfusion parameters and angiography., Results: Among 83 patients, median age 71 (maximum 89), median NIHSS 7 (range 1-30), 38 (46%) received alteplase, 41 (49%) had died or were dependent at 3 months. Most baseline imaging was CT (76%); follow-up was MR (79%) despite both being available acutely. At presentation, perfusion lesion size varied considerably between parameters (p<0.0001); 40 (48%) had arterial occlusion. Arterial occlusion and baseline perfusion lesion extent were both associated with baseline NIHSS (p<0.0001). Recanalisation by 72 h was associated with 1 month NIHSS (p=0.0007) and 3 month functional outcome (p=0.048), whereas tissue reperfusion, using even the best perfusion parameter, was not (p=0.11, p=0.08, respectively)., Conclusion: Early recanalisation on angiography appeared to predict clinical outcome more directly than did tissue reperfusion. Acute assessment with CT and follow-up with MR was practical and feasible, did not preclude image analysis, and would enhance trial recruitment and generalisability of results.

Purpose: There is a shortage of human eye tissue available for scientists, and it is unknown how willing ophthalmic patients are to donate their eyes for research. Therefore, we assessed eye patient and family member attitudes regarding the establishment of an eye donation registry for research purposes., Materials and Methods: Surveys were distributed to consecutive patients attending the clinics of an academic ophthalmology practice over a period of 8 days. This survey consisted of questions about demographic information of the participant, attitudes regarding eye donation and attitudes regarding a registry for research-specific eye donation. An additional nested survey was administered to family members who accompanied survey participants., Results: A total of 207 patients and 76 accompanying family members returned their respective surveys. Of the patients, 55% indicated that they would consider joining a proposed eye donation registry for research, 30% were undecided and 15% would not consider joining (n = 193). Over 95% of family members indicated that they would support their relative's decision to enroll in the registry (n = 74). Of the potential donors, 41% indicated they would most prefer to learn about the registry from their eye doctor and 37% from a pamphlet (n = 180)., Conclusions: A majority of patients with eye disease and their family members support the idea of establishing an advance-directive eye donation registry for research. This registry for research donors could be incorporated into the current eye donation registry. Such an addendum would bridge the current disconnect between ophthalmic patients who want to donate their eyes for research on their disease (and are ineligible to donate for corneal transplantation) and scientists who need more human eye tissue for experimentation.

Background: Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials.Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely., Design: BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0-3., Discussion: The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755).