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Background: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality., Methods: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual., Findings: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059)., Interpretation: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis., Funding: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation., Competing Interests: Declaration of interests SBC received grant funding from the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada (HSFC), and the British Heart Foundation (BHF) to complete the TEMPO-2 study. Boehringer Ingelheim provided off-the-shelf study drug (tenecteplase) for the study. JFA has received public research grants from the Spanish Ministry of Science, the regional health department, the European Commission, and a private research grant from AstraZeneca. He has received consultant or speaker fees from Pfizer-BMS, Medtronic, and Amgen, and travel support from Daiichi-Sankyo. KSB reports speaker fees from Boehringer Ingelheim and AstraZeneca. LC has received consulting or speakers fees from Roche. JF reports speaker fees from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Pfizer, Sankyo, and Daiichi. AG reports a grant from Microvention; speaker fees from Alexion, Biogen, and Servier Canada; and stock options for SnapDx and Collavidence. DG reports honoraria from Boehringer Ingelheim, Ipsen, and Eisai. MG reports grant funding from Medtronic and Cerenovus and consulting fees from Mentice, CSL Behring, MicroVention, and Medtronic. TSF participated in an advisory board for Roche. FL reports speaker fees and travel support from Boehringer Ingelheim. BKM has been paid honoraria from Boehringer Ingelheim and Roche. MM has received honoraria from Boehringer Ingelheim for participation at an advisory board on the approval of tenecteplase for treatment of acute ischaemic stroke. SOM has received speaker fees from Boehringer, Medtronic, Penumbra, Bayer, Pfizer, Novartis, Novo Nordisk, Servier, and Daiichi Sankyo. KWM reports grant funding from the BHF, and the Stroke Association; consultancy fees from Boehringer Ingelheim, Biogen, IschaemaView; lecture fees from Boehringer Ingelheim, IschaemaView, and Brainomix; and non-financial support (drug supply for ATTEST-2 trial) from Boehringer Ingelheim. MWP is on Boehringer Ingelheim Advisory Board for Metalyse in stroke. AP received speaker fees from Boehringer Ingelheim and travel support from AstraZeneca for attending a meeting. OMP-N has received speaker fees from Boehringer Ingelheim and AstraZeneca. RS is part funded by the UCLH Biomedical Research Centre. DS reports an unrestricted educational grant from Boehringer Ingelheim. MIW reports sponsorship or financial assistance to support attendance at scientific meetings from Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo UK, and Bayer; honoraria for lectures given at education meetings from Boehringer Ingelheim, Bristol Myers Squibb, and AstraZeneca; and payment for participation in advisory panels from Boehringer Ingelheim and Daiichi Sankyo UK. DJW is the Co-principal Investigator for Health Research Board of Ireland, Award–Improving Pathways for Acute Stroke and Rehabilitation. AYXY reports salary support from the HSFC. MDH reports grant funding from CIHR, HSFC, Alberta Innovates, and study drug from Boehringer Ingelheim; grants from NoNo and Medtronic; consulting fees from Sun Pharma Brainsgate; and a DSMB member role on many stroke clinical trials., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Intracerebral haemorrhage (ICH) is a severe clinical consequence of cerebral small vessel disease (SVD), but associations between renal impairment and SVD in patients with ICH have not been fully characterised., Methods: Using data from the CROMIS-2 ICH observational study, we compared SVD neuroimaging markers and total burden (score 0-3) identified using CT brain imaging in patients with and without renal impairment (estimated glomerular filtration rate, eGFR<60). We assessed functional outcome at 6-month follow-up using the modified Rankin scale., Results: 1027 participants were included (mean age 72.8, 57.1% male); 274 with and 753 without renal impairment. 18.7% of the eGFR<60 group had moderate-to-severe SVD burden (score 2-3), compared with 14.0% of those with eGFR>60 (p = 0.039). SVD burden was associated with renal impairment after adjusting for hypertension (OR 1.36, 95% CI 1.04-1.77, p = 0.023), but not after adjusting for age. Cerebral atrophy was more prevalent in patients with eGFR<60 (81.2% vs. 72.0%, p = 0.002), as were WMH (45.6% vs. 36.6%, p = 0.026). Neither was associated with renal function after adjusting for age and vascular risk factors. Renal impairment was associated with functional outcome (OR 0.65, 95% CI 0.47-0.89, p = 0.007), but not after adjusting for age, pre-morbid function and comorbidities (OR 0.95, 95% CI 0.65-1.38, p = 0.774)., Conclusion: In acute ICH, renal impairment is associated with a higher cerebral SVD burden independent of hypertension, but not age. Reduced eGFR is associated with worse functional outcome, but not independent of age and comorbidities. Since CT has limited sensitivity to detect SVD severity and distribution, further studies including MRI are needed., Competing Interests: Declaration of Competing Interest The authors report that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To examine whether non-adherent African American patients with glaucoma who received a question prompt list and video intervention were more likely to be given treatment options, have their input included into treatment regimens, and rate their providers as using more of a participatory decision-making style., Methods: African American patients with glaucoma taking one or more glaucoma medications and reported being non-adherent were randomized to a pre-visit video and glaucoma question prompt list intervention or usual care., Results: 189 African American patients with glaucoma participated. Providers gave patients treatment choices during 5.3% of visits and included patient input into treatment regimen decisions during 2.1% of visits. Male patients and patients with more years of education were significantly more likely to rate their providers as using more of a participatory decision-making style., Conclusion: African American patients with glaucoma rated their providers high on using a participatory decision-making style. Yet, providers infrequently presented non-adherent patients with medication treatment options, and it was rare for providers to include patient input into treatment decisions., Practice Implications: Providers should provide non-adherent patients with different glaucoma treatment options. Non-adherent African American patients with glaucoma should be encouraged to ask their providers for different medication treatment options., Competing Interests: Conflict of interest There are no competing interest that relate to any authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Total small vessel disease (SVD) score and cerebral amyloid angiopathy (CAA) score are magnetic resonance imaging-based composite scores built to preferentially capture deep perforator arteriopathy-related and CAA-related SVD burden, respectively. Non-lobar intracerebral haemorrhage (ICH) is related to deep perforator arteriopathy, while lobar ICH can be associated with deep perforator arteriopathy or CAA; however, the associations between ICH location and these scores are not established., Methods: In this post-hoc analysis from a prospective cohort study, we included 153 spontaneous non-cerebellar ICH patients. Wald test, univariable and multivariable logistic regression analysis were performed to investigate the association between each score (and individual score components) and ICH location., Results: Total SVD score was associated with non-lobar ICH location (Wald test: unadjusted, p = 0.017; adjusted, p = 0.003); however, no individual component of total SVD score was significantly associated with non-lobar ICH. CAA score was not significantly associated with lobar location (Wald test: unadjusted, p = 0.056; adjusted, p = 0.126); cortical superficial siderosis (OR 8.85 [95%CI 1.23-63.65], p = 0.030) and ≥ 2 strictly lobar microbleeds (OR 1.63 [95%CI 1.04-2.55], p = 0.035) were related with lobar ICH location, while white matter hyperintensities showed an inverse relation (OR 0.53 [95%CI 0.26-1.08; p = 0.081])., Conclusions: Total SVD score was associated with non-lobar ICH location. The lack of significant association between CAA score and lobar ICH may in part be due to the mixed aetiology of lobar ICH, and to the inclusion of white matter hyperintensities, a non-specific marker of SVD type, in the CAA score., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Patients waking up with stroke symptoms are often excluded from intravenous thrombolysis with alteplase (IV-tpa). The WAKE-UP trial, a European multicenter randomized controlled trial, proved the clinical effectiveness of magnetic resonance imaging-guided IV-tpa for these patients. This analysis aimed to assess the cost-effectiveness of the intervention compared to placebo., Methods: A Markov model was designed to analyze the cost-effectiveness over a 25-year time horizon. The model consisted of an inpatient acute care phase and a rest-of-life phase. Health states were defined by the modified Rankin Scale (mRS). Initial transition probabilities to mRS scores were based on WAKE-UP data and health state utilities on literature search. Costs were based on data from the University Medical Center Hamburg-Eppendorf, literature, and expert opinion. Incremental costs and effects over the patients' lifetime were estimated. The analysis was conducted from a formal German healthcare perspective. Univariate and probabilistic sensitivity analyses were performed., Results: Treatment with IV-tpa resulted in cost savings of €51 009 and 1.30 incremental gains in quality-adjusted life-years at a 5% discount rate. Univariate sensitivity analysis revealed incremental cost-effectiveness ratio being sensitive to the relative risk of favorable outcome on mRS for placebo patients after stroke, the costs of long-term care for patients with mRS 4, and patient age at initial stroke event. In all cases, IV-tpa remained cost-effective. Probabilistic sensitivity analysis proved IV-tpa cost-effective in >95% of the simulations results., Conclusions: Magnetic resonance imaging-guided IV-tpa compared to placebo is cost-effective in patients with ischemic stroke with unknown time of onset., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: There is uncertainty about the clinical benefit of admission to critical care after spontaneous intracerebral haemorrhage (ICH)., Purpose: We investigated factors associated with critical care admission after spontaneous ICH and evaluated associations between critical care and 6-month functional outcome., Methods: We included 825 patients with acute spontaneous non-traumatic ICH, recruited to a prospective multicenter observational study. We evaluated the characteristics associated with critical care admission and poor 6-month functional outcome (modified Rankin Scale, mRS > 3) using univariable (chi-square test and Wilcoxon rank-sum test, as appropriate) and multivariable analysis., Results: 286 patients (38.2%) had poor 6-month functional outcome. Seventy-seven (9.3%) patients were admitted to critical care. Patients admitted to critical care were younger (p < 0.001), had lower GCS score (p < 0.001), larger ICH volume (p < 0.001), more often had intraventricular extension (p = 0.008) and underwent neurosurgery (p < 0.001). Critical care admission was associated with poor functional outcome at 6 months (39/77 [50.7%] vs 286/748 [38.2%]; p = 0.034); adjusted OR 2.43 [95%CI 1.36-4.35], p = 0.003), but not with death (OR 1.29 [95%CI 0.71-2.35; p = 0.4). In ordinal logistic regression, patients admitted to critical care showed an OR 1.47 (95% CI 0.98-2.20; p = 0.07) for a shift in the 6-month modified Rankin Scale., Conclusions: Admission to critical care is associated with poor 6-month functional outcome after spontaneous ICH but not with death. Patients admitted to critical care were a priori more severely affected. Although adjusted for main known predictors of poor outcome, our findings could still be confounded by unmeasured factors. Establishing the true effectiveness of critical care after ICH requires a randomised trial with clinical outcomes and quality of life assessments., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers., Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903., Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I 2 =27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024)., Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The chromosome 9 open reading frame 72 (C9orf72) GGGGCC repeat expansion has been associated with several diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. It has also been associated with increased white matter changes in frontotemporal dementia and risk of cognitive impairment in ALS. Dementia is common both before and after intracerebral hemorrhage (ICH). Because the mechanisms of cognitive impairment in patients with ICH are uncertain, we investigated whether C9orf72 could influence dementia risk in this patient group. Therefore, we genotyped 1010 clinically characterized ICH cases and 2147 population controls in comparison with prior data of dementia and ALS cases. We did not find any association between C9orf72 repeat expansion and repeat size with ICH compared with controls or with dementia when assessing ICH patients only. The frequency of C9orf72 expansions in our series of individuals born in 1946 (2/2147) and other U.K. controls was age dependent, decreasing with increasing age, highlighting the high age-dependent penetrance of this expansion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine the effectiveness of an online video intervention in improving self-efficacy and eye drop application technique in glaucoma patients., Methods: We randomized ninety-two patients with primary open-angle glaucoma, all who self-administer their eye drops, to either watch the 4-minute Meducation® eye drop technique video in the intervention group, or a nutrition video in the control group. We assessed five eye drop technique steps using objective video recordings at baseline, immediately after watching the video, and 1 month later. We used linear regression models to determine whether the intervention group had better self-efficacy and technique than the control group., Results: Adjusted for baseline technique and other covariates, eye drop technique averaged 0.73 steps better in intervention patients than controls immediately after the video (p = 0.003) and 0.63 steps better at 1 month (p = 0.01). Adjusted for baseline self-efficacy, intervention patients had better eye drop technique self-efficacy than controls immediately after the video (p = 0.02) and at 1 month (p = 0.02)., Conclusion: A short educational video can significantly improve glaucoma patients' short-term self-efficacy and eye drop technique., Practice Implications: Videos may provide an inexpensive, convenient way to deliver eye drop technique education in any provider's office or online., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to: (a) describe the extent to which ophthalmologists and glaucoma patients discuss vision quality-of-life during office visits, and (b) examine the association between patient and ophthalmologist characteristics and provider-patient communication about vision quality-of-life., Methods: Patients with glaucoma who were newly prescribed or on glaucoma medications were recruited at six ophthalmology clinics. Patients' visits were video-tape recorded and quality-of-life communication variables were coded. Generalized estimating equations were used to analyze the data., Results: Two hundred and seventy-nine patients participated. Specific glaucoma quality-of-life domains were discussed during only 13% of visits. Older patients were significantly more likely to discuss one or more vision quality-of-life domains than younger patients. African American patients were significantly less likely to make statements about their vision quality-of-life and providers were less likely to ask them one or more vision quality-of-life questions than non-African American patients., Conclusion: Eye care providers and patients infrequently discussed the patient's vision quality-of-life during glaucoma visits. African American patients were less likely to communicate about vision quality-of-life than non-African American patients., Practice Implications: Eye care providers should make sure to discuss vision quality-of-life with glaucoma patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients., Methods: We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale [NIHSS] score ≥6 and modified Rankin Scale score 2-4) 6-60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov, number NCT01151124., Findings: 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60-82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6-8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points., Interpretation: Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients., Funding: ReNeuron Limited., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

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.)

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.)

Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood-brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a cross-validation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To test an educational intervention targeted to health literacy level with the goal of improving glaucoma medication adherence., Methods: One hundred and twenty-seven veterans with glaucoma were randomized to glaucoma education or standard care. The intervention included a video scripted at a 4th, 7th, or 10th grade level, depending on the subject's literacy level. After six months, the number of days without glaucoma medicine (DWM) according to pharmacy records for the intervention and control groups was compared., Results: The number of DWM in the six months following enrollment was similar for control and intervention groups (intervention, n=67, DWM=63 ± 198; standard care, n=60, DWM=65 ± 198; p=0.708). For each subgroup of literacy (adequate, marginal, inadequate), subjects in the intervention group experienced less mean DWM than subjects in the control group and the effect size (ES) increased as literacy decreased: adequate literacy, ES 0.069; marginal, ES 0.183, inadequate, ES 0.363. Decreasing health literacy skills were associated with decreasing self-reported satisfaction with care (slope=0.017, SE=0.005, p=0.002)., Conclusions: Patients with decreased health literacy skills may benefit from educational efforts tailored to address their health literacy level and learning style., Practice Implications: Providers should consider health literacy skills when engaging in glaucoma education., (Published by Elsevier Ireland Ltd.)

The prospects for stem cell-derived therapy in stroke look promising, with a myriad of cell therapy products developed from brain, blood, bone marrow, and adipose tissue in early clinical development. Eight clinical trials have now reported final results, and several are currently registered recruiting patients or pending to start. Products passing the safety hurdle are recruiting patients for large efficacy studies. Besides identifying the most appropriate cell type, other issues to resolve include optimal timing for intervention, optimal delivery route, cell dose, patient selection, relevant clinical endpoints, and monitoring for effectiveness, to advance cell therapy through the hurdles of clinical research. In this chapter, we present the products and strategies used in the current cell therapy trials in ischemic stroke, provide an update on relevant preclinical research, and discuss the vital developments still needed to advance their clinical application as a future therapeutic option., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Central corneal thickness (CCT) has emerged as an important predictive factor for the development of glaucomatous damage. Although a child's cornea reaches adult thickness by the age of 3, little has been reported about normal CCT measurements in eyes of children. We wished to test the hypotheses that (1) there is a correlation between increasing CCT and increasing intraocular pressure (IOP) in the eyes of children, (2) the CCT in the eyes of children with ocular hypertension is greater than that in eyes of normal pediatric subjects, and (3) the average CCT of black children is less than that of white children., Methods: We performed a retrospective chart review of 69 pediatric patients seen in the office of one ophthalmologist between January 1997 and December 2001 in whom CCT was measured by ultrasound pachymetry. We categorized the subjects into diagnostic groups of controls, glaucoma, glaucoma suspects, and ocular hypertension based on IOP, cup-to-disc ratio, and visual field parameters., Results: The average CCT for the control patients was 555+/-37 microm; for patients with glaucoma, it was 563+/-33 microm; for glaucoma suspects, 559+/-39 microm; and for those with ocular hypertension, 595+/-39 microm. The difference between the control and ocular hypertensive groups was significant (P<0.02). The difference in CCT between the black control subjects and the white ones (537+/-36 microm vs. 564+/-28 microm) was not statistically significant (P = 0.125)., Conclusions: Central corneal thickness is greater in children with ocular hypertension than in control subjects or those with glaucoma, and the values for CCT in these children correlate closely with values reported for adults. Corneas of black children may be thinner than the corneas of white children.

Background: Magnesium is neuroprotective in animal models of stroke, and findings of small clinical pilot trials suggest potential benefit in people. We aimed to test whether intravenous magnesium sulphate, given within 12 h of stroke onset, reduces death or disability at 90 days., Methods: 2589 patients were randomised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h, or matching placebo. Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90. Secondary outcomes were mortality and death or disability, variously defined as Barthel score less than 95, Barthel score less than 60, and modified Rankin scale more than 1. Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h, ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non-cortical strokes. Intention-to-treat and efficacy analyses were done., Findings: The efficacy dataset included 2386 patients. Primary outcome was not improved by magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly higher in the magnesium-treated group than in the placebo group (hazard ratio 1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment effect. Planned subgroup analyses showed benefit of magnesium in non-cortical strokes (p=0.011) whereas greater benefit had been expected in the cortical group., Interpretation: Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly, although it may be of benefit in lacunar strokes.

The differentiation of cerebral infarction and cerebral haemorrhage is the most important first step in the management of acute stroke, because clinical management of the two disorders differs substantially. The Guy's Hospital and Siriraj stroke diagnostic scores were developed to aid clinicians in this decision. We have tested the performance of the two scores on a group of 1059 patients admitted to the acute stroke unit (ASU) at the Western Infirmary, Glasgow, with suspected stroke between May, 1990, and December, 1993. The diagnosis was confirmed as stroke by computed tomography (CT) scanning or necropsy (n = 10) in 991 patients. For each clinical score we subjectively identified the cut-off point that maximised sensitivity to cerebral haemorrhage with the smallest loss of specificity. At its optimum cut-off point the Guy's Hospital score had a sensitivity for the diagnosis of haemorrhage of 70% and specificity of 64%. The corresponding figures for the Siriraj score at its optimum cut-off point were 68% sensitivity and 64% specificity. The overall predictive accuracy of both scores was 64%. The greater complexity of the Guy's Hospital score (thirteen variables included) did not result in substantially superior performance to the Siriraj score (five variables). This validation study suggests that neither score is useful for exclusion of haemorrhage before anticoagulant treatment is initiated or as a diagnostic screening procedure for trials of low-risk treatments such as aspirin. Our findings emphasise the need for routine CT scanning in this setting, since this method remains the most accurate for differentiating between haemorrhage and infarction.

A pathogenetic role in thrombotic disease, particularly in young people, has been postulated for anticardiolipin antibody (ACA). We have carried out a prospective controlled study of 262 unselected patients with acute stroke and 226 controls to assess the prevalence and relation to age and vascular risk factors of ACA. Titres of IgG, IgA, or IgM ACA were above the upper normal limit in 38% of patients. The proportions of patients and controls with raised titres did not differ significantly (13 vs 8% IgG, 22 vs 29% IgA, 11 vs 7% IgM). IgG titres were higher among patients than among controls (mean 3.88 vs 2.86 u/mL [95% CI for difference 0.62-0.87], p = 0.0004), whereas IgA and IgM titres were lower in patients than in controls (IgA 4.82 vs 5.98 u/mL [1.12-1.60], p = 0.01; IgM 3.00 vs 3.64 u/mL [1.01-1.45], p = 0.04). However, within age tertiles the only significant difference between patients and controls for IgG ACA was in the oldest tertile. Analysis by number of risk factors for stroke showed a significant difference between the groups only for subjects with one risk factor. IgA and IgM ACA titres were higher among controls only in those with no vascular risk factors. We found no evidence to support the hypothesis that ACA is an independent risk factor for stroke in young people. The increase in IgG titre with age and number of vascular risk factors in stroke patients suggests that ACA may be a non-specific accompaniment of vascular disease. Routine testing for ACA in stroke patients is not justified.