[Show abstract][Hide abstract] ABSTRACT: Background The risks of intracranial haemorrhage (ICH) post intra-arterial therapy (IAT) for stroke are not well understood. We aimed to study the influence of recanalization status post IAT for anterior circulation stroke and posterior circulation stroke on ICH development. Methods Retrospective analysis of 193 patients in a prospectively collected database of IAT stroke patients was performed. Successful recanalization was defined as a Thrombolysis in Cerebral Infarction Score of 2b or 3 and symptomatic ICH (SICH) as parenchymal hematoma type 2 (PH2) with neurological deterioration. The association between the recanalization status and ICH/SICH was investigated using logistic regression models adjusted for baseline characteristics selected by univariate analyses. Results One hundred and thirty-six patients had successful recanalization post procedure, 41 patients developed ICH and 10 patients SICH. There was a statistically significant baseline imbalance between the groups with and without successful recanalization on gender, baseline National Institute of Health Stroke Scale (NIHSS) score, the use of intravenous tPA and intra-arterial urokinase (p <0.05). Logistic regression analysis adjusted for the above variables and the time to digital subtraction angiography demonstrated a statistically significant association between successful recanalization and ICH (odds ratio 0.42; 95 % CI 0.19, 0.95; p = 0.04). Conclusion Successful recanalization post endovascular therapy is statistically significantly and negatively associated with ICH.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time.
Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ≤18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration.
Forty-seven patients were imaged with (11)C-PiB positron emission tomography. There was an increase in (11)C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of (11)C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated (11)C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of (11)C-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04).
There was no significant increase in (11)C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric (11)C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased β-amyloid deposition ≤18 months after stroke.
[Show abstract][Hide abstract] ABSTRACT: The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality.
[Show abstract][Hide abstract] ABSTRACT: Objective To use admission inpatient glycated hemoglobin (HbA1c) testing to help investigate the prevalence of unrecognized diabetes, the cumulative prevalence of unrecognized and known diabetes, and the prevalence of poor glycemic control in both. Moreover, we aimed to determine the 6-month outcomes for these patients. Finally, we aimed to assess the independent association of diabetes with these outcomes.
Research, design, and methods Prospective observational cohort study conducted in a tertiary hospital in Melbourne, Australia.
Patients A cohort of 5082 inpatients ≥54 years admitted between July 2013 and January 2014 underwent HbA1c measurement. A previous diagnosis of diabetes was obtained from the hospital medical record. Patient follow-up was extended to 6 months.
Results The prevalence of diabetes (known and unrecognized) was 34%. In particular, we identified that unrecognized but HbA1c-confirmed diabetes in 271 (5%, 95% CI 4.7% to 6.0%) patients, previously known diabetes in 1452 (29%, 95% CI 27.3% to 29.8%) patients; no diabetes in 3359 (66%, 95% CI 64.8–67.4%) patients. Overall 17% (95% CI 15.3% to 18.9%) of patients with an HbA1c of >6.5% had an HbA1c ≥8.5%. After adjusting for age, gender, Charlson Index score, estimated glomerular filtration rate, and hemoglobin levels, with admission unit treated as a random effect, patients with previously known diabetes had lower 6-month mortality (OR 0.69, 95% CI 0.56 to 0.87, p=0.001). However, there were no significant differences in proportions of intensive care unit admission, mechanical ventilation or readmission within 6 months between the 3 groups.
Conclusions Approximately one-third of all inpatients ≥54 years of age admitted to hospital have diabetes of which about 1 in 6 was previously unrecognized. Moreover, poor glycemic control was common. Proportions of intensive care unit admission, mechanical ventilation, or readmission were similar between the groups. Finally, diabetes was independently associated with lower 6-month mortality.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Cerebral atrophy after stroke is associated with poor functional outcome. The prediction and prevention of post-stroke brain atrophy could therefore represent a target for neurorestorative therapies. We investigated the associations between peri-infarct metabolite concentrations measured by quantitative MRS and brain volume change in the infarct hemisphere after stroke.
Twenty patients with ischemic stroke were enrolled. Patients underwent 3T-MRI within 1 week of onset, and at 1 and 3 months. At the baseline scan, an MRS voxel was placed manually in the peri-infarct area and another in the corresponding contralateral region. Volumetric analysis of T1 images was performed using two automated processing packages. Changes in gray and white matter volume were assessed as percentage change between 1 and 3 months.
Mean concentrations (institutional units) of N-acetylaspartic acid (NAA) (6.1 vs 7.0, p = 0.039), total creatine (Cr+PCr) (5.4 vs 5.8, p = 0.043), and inositol (4.5 vs 5.0, p = 0.014), were significantly lower in the peri-infarct region compared with the contralateral hemisphere. There was a significant correlation between baseline peri-infarct NAA and white matter volume change in the infarct hemisphere between 1 and 3 months, with lower NAA being associated with subsequent white matter atrophy (Spearman's rho = 0.66, p = 0.010). The baseline concentration of Cr+PCr was also significantly correlated with white matter atrophy in the infarct hemisphere (Spearman's rho = 0.59, p = 0.027). Both of these associations were significant after adjustment for the false discovery rate and were validated using the secondary volumetric method.
MRS may be useful in the prediction of white matter atrophy post-stroke and in the testing of novel neurorestorative therapies.
[Show abstract][Hide abstract] ABSTRACT: Aims:
To assess the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and longitudinally in people with type 2 diabetes.
Adults with type 2 diabetes attending Austin Health, Melbourne, with≥3 prospective GFR measurements were included in this retrospective study. Plasma disappearance rate of DTPA (diethylene-triamine-penta-acetic acid) was used to calculate measured GFR (mGFR) and compared to estimated GFR (eGFR). The agreement between mGFR and eGFR was estimated using Intraclass Correlation Coefficient (ICC).
152 patients had a median of 4 (IQR: 3, 5) mGFR measurements over a period of 11years (IQR: 9, 12). The difference between mGFR and eGFR increased proportionally to the magnitude of the GFR, increasing by 0.2ml/min/1.73m(2) for every 1ml/min/1.73m(2) increase in mGFR, indicative of proportional bias. At lower mGFR levels, eGFR overestimated mGFR, and at higher mGFR levels, eGFR underestimated mGFR. There was a significant association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR.
The CKD-EPI formula underestimates mGFR and the rate of decline of mGFR in patients with type 2 diabetes with an mGFR greater than 60ml/min/1.73m(2). The association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR warrants further study.
Journal of diabetes and its complications 09/2015; DOI:10.1016/j.jdiacomp.2015.08.025 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: sec> Objective The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). Design AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Setting Acute stroke units at 44 hospitals in 8 countries. Participants The first 20 000 patients screened for AVERT, of whom 1158 were recruited and randomised. Model We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. Results The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). Conclusions A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). </sec
BMJ Open 08/2015; 5(8). DOI:10.1136/bmjopen-2015-008378 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The hyperdense middle cerebral artery sign [HMCAS]and hyperdense basilar sign [HBAS]are associated with poor outcome with thrombolysis [t-PA). Intra-arterial [IA]therapy is sometimes used in the management of acute anterior circulation strokes in addition to t-PA. The utility of these signs in stratifying outcomes with IA therapy is limited. We compared recanalisation rates with IA therapy in patients with and without the signs.
[Show abstract][Hide abstract] ABSTRACT: Both time of the day and season have been shown to have a significant effect on stroke incidence. In contrast, the role played by the moon has been little studied. We aimed to investigate the potential association of the lunar phase with the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)], adjusted by circadian and seasonal variations. Consecutive stroke admissions to the Royal Melbourne Hospital (RMH) were analyzed from 2004–2011. Of 6252 patients, 4085 (65.3%) had confirmed dates and hour of the day. Of these, 632 (15.5%) had ICH, 658 (16.1%) presented with TIA and 2202 (53.9%) had IS. There were also 593 (14.5%) stroke mimics. We measured the association of stroke incidence with a particular lunar phase using an incidence rate ratio (IRR) with 95% confidence intervals (CI) using Poisson regression model (new moon set as reference). Compared with new moon phase, ICHs occurred significantly more during the first quarter (IRR, 1.55; 95%CI, 1.04 to 2.30; p = 0.03). More TIAs were observed during the first quarter and full moon than in new moon (IRR, 1.69; 95%CI, 1.16 to 2.46; p = 0.01; IRR, 1.52; 95%CI, 0.00 to 2.31; p = 0.05; respectively). Both ICH and TIA occurrence slightly decreased as lunar illumination increased (IRR, 0.99; 95%CI, 0.99 to 1.00; p = 0.01; IRR, 0.99; 95%CI, 0.99 to 1.00; p = 0.04; respectively). No association was found between lunar phase or illumination and IS. All stroke subtypes were less likely to happen between 12AM and 6AM than the remaining 18 h of the day. IS occurrence was significantly higher during the spring than summer (IRR, 1.14; 95%CI, 1.02 to 1.28; p = 0.03). For the patients older than 65 years, incidence of both ICH and IS was higher in spring than in summer (IRR, 1.33; 95%CI, 1.01 to 1.74; p = 0.04; IRR, 1.22; 95%CI, 1.06 to 1.39; p = 0.005; respectively). The lunar phase and illumination are associated with both ICH and TIA incidence. These findings should be tested on other stroke databases.
Chronobiology International 07/2015; 32(7). DOI:10.3109/07420528.2015.1049614 · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hyperdense artery sign (HAS) on CT brain scan is an assumed radiological marker of acute intra-arterial thrombotic occlusion. However, the relationship between HAS between time of stroke onset has not been adequately investigated, leading to uncertainty regarding its validity as a marker of acute ischaemia. We attempted to determine if the presence of the hyperdense artery sign is associated with time from stroke onset.
Retrospective cross-sectional study conducted in a tertiary referral centre. Consecutive patients with acute ischaemic stroke and confirmed middle cerebral arterial occlusion on initial CT angiogram from 2007–2011 were included. Visual estimation and manual measurement of Hounsfield units of affected and corresponding non-affected artery on non-contrast CT was completed and mean density was calculated from four separate readings. Primary outome measures were Time from stroke onset and HAS on both visual estimation and the ratio of mean value in Hounsfield Units (HU) of affected to non-affected artery.
One hundred and fifty-four subjects with confirmed arterial occlusion on CT Angiogram were included in the study. There were no significant differences in age distribution or vascular risk factor presence between subjects with or without HAS. Subjects with HAS were less likely to be male (50.9 % vs 70.8 %, p = 0.02).) HAS was found in 106 (68.8 %) of all subjects. Median NIHSS score at presentation was significantly higher in the HAS group (17 vs 12, p = 0.02). No statistically significant association between HAS and stroke onset time or density ratio between affected and non-affected artery was detected overall within either the first 24-h or on subgroup analysis of those in the first 4.5-h. A small subgroup of three patients with stroke onset greater than 24-h all had absent HAS.
No evidence of a correlation between time of stroke onset and presence of a HAS within the first 24-h post acute ischaemic stroke was identified. The HAS was associated with a higher NIHSS score at presentation.
[Show abstract][Hide abstract] ABSTRACT: Background and aim: In humans, inactivity after stroke is associated with accelerated bone loss. The aim of this study was to investigate skeletal effects of brain infarct, using a proven animal model.
Hypothesis: post-stroke, skeletal parameters of left and right femurs would be compromised, but physical activity unaffected, to suggest a skeletal effect of brain infarct.
Methods: Spontaneously-hypertensive male rats, aged 15 weeks, randomised to stroke (right middle cerebral artery occlusion, n=12) or sham surgery (n=8). Impairment testing (stroke behaviours, ladder walk) and activity monitoring (proportion of time active) were undertaken prior to cull at four weeks. Trabecular and cortical parameters of distal regions of both femurs were determined by Micro-CT (10.5µm resolution). Study was approved and managed according to Austin Health Animal Ethics Committee.
Results: Stroke animals displayed impaired left hindlimbs, but activity did not differ between groups. Non-parametric analyses showed no between-group differences in trabecular (primary outcome) or cortical parameters of left femurs. However, between-group differences were observed in right femurs: stroke animals had lower trabecular connective density (median 194.1 (IQR 182.9,230.0) v 206.0 (195.9,226.2),p=0.03), cortical bone volume fraction (85.8% (83.6,86.0) v 88.1 (86.4,89.1) p=0.02) and material density (951.8mgHA/mm3 (943.3,958.1) v 973.4(969.2,981.7), p=0.01). Stroke impairments were not associated with these parameters.
Conclusion: Stroke animals had compromised bone parameters of non-paretic legs, but not paretic legs compared to shams, despite no observed differences in activity or associations with impairments. Investigation of limb use and weight bearing symmetry using this model is warranted to better understand drivers of post-stroke bone loss.
The European Stroke Organisation Conference, Glasgow, Scotland; 04/2015
[Show abstract][Hide abstract] ABSTRACT: Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods.
Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1 week of onset and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements.
Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions.
Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions.
[Show abstract][Hide abstract] ABSTRACT: Stroke survivors experience accelerated bone loss and increased fracture risk, particularly in paretic weight bearing limbs. Understanding how these changes unfold and their relationship to stroke severity and physical activity could help in the development of targeted interventions to prevent or reduce the severity of these outcomes. The primary aim of this study is to investigate the time course and magnitude of changes in volumetric bone mineral density within the first year after stroke, and to examine relationships with physical activity and motor recovery.
This is a prospective, observational study of 43 nondiabetic, nonambulant adults with first ever hemispheric stroke.
The primary outcome was the difference in six-month change of total volumetric bone mineral density between paretic and nonparetic distal tibiae, measured at 7% of bone length site using high-resolution peripheral quantitative computed tomography.
The secondary outcomes are cortical and trabecular volumetric bone mineral density, cortical thickness, and total and cross-sectional areas of distal tibiae and radii of paretic and nonparetic limbs. Also included are total body and regional bone mineral density derived using dual-energy X-ray absorptiometry, physical activity measured using accelerometry, and motor recovery (Chedoke McMaster Stroke Assessment).
Measuring the timing and magnitude of changes to volumetric bone mineral density and bone structure from immediately after stroke, and relationships between these changes with physical activity and motor recovery will provide the basis for targeted interventions to reduce fracture risk in stroke survivors.
International Journal of Stroke 04/2015; 10(3):396 - 399. DOI:10.1111/ijs.12228 · 3.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes.
We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days.
The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.
In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).
New England Journal of Medicine 02/2015; 372(11). DOI:10.1056/NEJMoa1414792 · 55.87 Impact Factor