Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Using remote sensing to assess peatland resilience by estimating soil surface moisture and drought recovery.

Peatland areas provide a range of ecosystem services, including biodiversity, carbon storage, clean water, and flood mitigation, but many areas of peatland in the UK have been degraded through human land use including drainage. Here, we explore whether remote sensing can be used to monitor peatland resilience to drought. We take resilience to mean the rate at which a system recovers from perturbation; here measured literally as a recovery timescale of a soil surface moisture proxy from drought lowering. Our objectives were (1) to assess the reliability of Sentinel-1 Synthetic Aperture Radar (SAR) backscatter as a proxy for water table depth (WTD); (2) to develop a method using SAR to estimate below-ground (hydrological) resilience of peatlands; and (3) to apply the developed method to different sites and consider the links between resilience and land management. Our inferences of WTD from Sentinel-1 SAR data gave results with an average Pearson's correlation of 0.77 when compared to measured WTD values. The 2018 summer drought was used to assess resilience across three different UK peatland areas (Dartmoor, the Peak District, and the Flow Country) by considering the timescale of the soil moisture proxy recovery. Results show clear areas of lower resilience within all three study sites, which often correspond to areas of high drainage and may be particularly vulnerable to increasing drought severity/events under climate change. This method is applicable to monitoring peatland resilience elsewhere over larger scales, and could be used to target restoration work towards the most vulnerable areas.

A model of gross primary productivity based on satellite data suggests formerly afforested peatlands undergoing restoration regain full photosynthesis capacity after five to ten years.

Peatlands are an important terrestrial carbon store, but disturbance has resulted in the degradation of many peatland ecosystems and caused them to act as a net carbon source. Restoration work is being undertaken but monitoring the success of these schemes can be difficult and costly using traditional field-based methods. A landscape-scale alternative is to use satellite data to assess the condition of peatlands and to estimate gaseous carbon fluxes. In this study we used Moderate Resolution Imaging Spectroradiometer (MODIS) products to model Gross Primary Productivity (GPP) over peatland sites at various stages of restoration. We found that the MOD17A2H GPP product overestimates GPP modelled from data collected by eddy covariance towers situated at two ex-forestry sites undergoing restoration towards blanket bog at the Forsinard Flows RSPB reserve, Scotland, UK (one full year of data), and a near-natural Atlantic blanket bog site in Glencar, Ireland (ten-year data series). We calibrated a Temperature and Greenness (TG) model for the Forsinard sites and found it to be more accurate than the MODIS GPP product at local scale. We also found that inclusion of a wetness factor using the Normalised Difference Water Index (NDWI) improved inter-annual accuracy of the model. This TGWa (annual Temperature, Greenness and Wetness) model was then applied to six control sites comprising near-natural bog across the reserve, and to six sites on which restoration began between 1998 and 2006. GPP from 2005 to 2016 was estimated for each site using the model. The resulting modelled trends are positive at all six restored sites, increasing by approximately 5.5 g C/m2/yr every year since restoration began in the Forsinard Flows reserve. The results suggest that peatland sites undergoing restoration at Forsinard Flows reach the carbon assimilation potential of near-natural bog sites between 5 and 10 years after restoration was begun.

Potential for using remote sensing to estimate carbon fluxes across northern peatlands - A review.

Peatlands store large amounts of terrestrial carbon and any changes to their carbon balance could cause large changes in the greenhouse gas (GHG) balance of the Earth's atmosphere. There is still much uncertainty about how the GHG dynamics of peatlands are affected by climate and land use change. Current field-based methods of estimating annual carbon exchange between peatlands and the atmosphere include flux chambers and eddy covariance towers. However, remote sensing has several advantages over these traditional approaches in terms of cost, spatial coverage and accessibility to remote locations. In this paper, we outline the basic principles of using remote sensing to estimate ecosystem carbon fluxes and explain the range of satellite data available for such estimations, considering the indices and models developed to make use of the data. Past studies, which have used remote sensing data in comparison with ground-based calculations of carbon fluxes over Northern peatland landscapes, are discussed, as well as the challenges of working with remote sensing on peatlands. Finally, we suggest areas in need of future work on this topic. We conclude that the application of remote sensing to models of carbon fluxes is a viable research method over Northern peatlands but further work is needed to develop more comprehensive carbon cycle models and to improve the long-term reliability of models, particularly on peatland sites undergoing restoration.

Small vessel disease and clinical outcomes after IV rt-PA treatment.

INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age±SD=68.7±15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.

Determinants of post-stroke cognitive impairment: analysis from VISTA.

BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs commonly and is linked with development of dementia. We investigated the relationship between demographic, clinical and stroke symptoms at stroke onset and the presence of PSCI at 1 and 3 years after stroke. METHODS: We accessed anonymized data from the Virtual International Stroke Trial Archive (VISTA), including demographic and clinical variables. Post-stroke cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤26. We assessed univariate relationships between baseline stroke symptoms and PSCI at 1 and 3 years following stroke, retaining the significant and relevant clinical factors as covariates in a final adjusted logistic regression model. RESULTS: We analysed data on 5435 patients with recent (median 33 days) stroke or transient ischaemic attack (TIA). Mean (±SD) age was 62.6 (±12.6) years; 3476 (65%) patients were male. Follow-up data were available for 2270 and 1294 patients at 1 and 3 years, respectively. At 1 year, 781 (34%) patients had MMSE≤26; at 3 years, 391 (30%) had MMSE≤26. After adjusting for age, stroke severity, hypertension, diabetes and type of qualifying event, initial stroke impairment (leg paralysis) was associated with increased rate of PSCI at 1 year (OR=1.62; 95% CI=1.20-2.20) and at 3 years (OR=1.95; 95% CI=1.23-3.09). Associations were consistent on subgroup analysis restricted to ischaemic stroke and transient ischaemic attack (N=4992). CONCLUSIONS: Besides well-known determinants of PSCI such as age, stroke severity and the presence of vascular risk factors, also leg paralysis is associated with subsequent of PSCI up to 3 years after stroke.

Traceable measurement and imaging of the complex permittivity of a multiphase mineral specimen at micron scales using a microwave microscope.

This paper describes traceable measurements of the dielectric permittivity and loss tangent of a multiphase material (particulate rock set in epoxy) at micron scales using a resonant Near-Field Scanning Microwave Microscope (NSMM) at 1.2GHz. Calibration and extraction of the permittivity and loss tangent is via an image charge analysis which has been modified by the use of the complex frequency to make it applicable for high loss materials. The results presented are obtained using a spherical probe tip, 0.1mm in diameter, and also a conical probe tip with a rounded end 0.01mm in diameter, which allows imaging with higher resolution (≈10µm). The microscope is calibrated using approach-curve data over a restricted range of gaps (typically between 1% and 10% of tip diameter) as this is found to give the best measurement accuracy. For both tips the uncertainty of scanned measurements of permittivity is estimated to be±10% (at coverage factor k=2) for permittivity ⪝10. Loss tangent can be resolved to approximately 0.001. Subject to this limit, the uncertainty of loss tangent measurements is estimated to be±20% (at k=2). The reported measurements inform studies of how microwave energy interacts with multiphase materials containing microwave absorbent phases.

Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment.

Short runs of atrial arrhythmia and stroke risk: a European-wide online survey among stroke physicians and cardiologists.

A recording of = 30 seconds is required to diagnose paroxysmal atrial fibrillation when using ambulatory ECG monitoring. It is unclear if shorter runs are relevant with regards to stroke risk. Methods An online survey of cardiologists and stroke physicians was carried out to assess current management of patients with short runs of atrial arrhythmia within Europe. Results Respondents included 311 clinicians from 32 countries. To diagnose atrial fibrillation, 80% accepted a single 12-lead ECG and 36% accepted a single run of > 30 seconds on ambulatory monitoring. Stroke physicians were twice as likely to accept < 30 seconds of arrhythmia as being diagnostic of atrial fibrillation (OR 2.43, 95% CI 1.19-4.98). They were also more likely to advocate anticoagulation for hypothetical patients with lower risk; OR 1.9 (95% CI 1.0-3.5) for a patient with CHA2DS2-VASc = 2. Conclusion Short runs of atrial fibrillation create a dilemma for physicians across Europe. Stroke physicians and cardiologists differ in their diagnosis and management of these patients.

Impact of heart rate on admission on mortality and morbidity in acute ischaemic stroke patients - results from VISTA.

BACKGROUND AND PURPOSE: Elevated heart rate (HR) is associated with worse outcomes in patients with cardiovascular disease. Its predictive value in acute stroke patients is less well established. We investigated the effects of HR on admission in acute ischaemic stroke patients. METHODS: Using the Virtual International Stroke Trials Archive (VISTA) database, the association between HR in acute stroke patients without atrial fibrillation and the pre-defined composite end-point of (recurrent) ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) and vascular death within 90 days was analysed. Pre-defined secondary outcomes were the composite end-point components and any death, decompensated heart failure and degree of functional dependence according to the modified Rankin Scale after 90 days. HR was analysed as a categorical variable (quartiles). RESULTS: In all, 5606 patients were available for analysis (mean National Institutes of Health Stroke Scale 13; mean age 67 years; mean HR 77 bpm; 44% female) amongst whom the composite end-point occurred in 620 patients (11.1%). Higher HR was not associated with the composite end-point. The frequencies of secondary outcomes were 3.2% recurrent stroke (n = 179), 0.6% TIA (n = 35), 1.8% MI (n = 100), 6.8% vascular death (n = 384), 15.0% any death (n = 841) and 2.2% decompensated heart failure (n = 124). Patients in the highest quartile (HR> 86 bpm) were at increased risk for any death [adjusted hazard ratio (95% confidence interval) 1.40 (1.11-1.75)], decompensated heart failure [adjusted hazard ratio 2.20 (1.11-4.37)] and worse modified Rankin Scale [adjusted odds ratio 1.29 (1.14-1.52)]. CONCLUSIONS: In acute stroke patients, higher HR (>86 bpm) is linked to mortality, heart failure and higher degree of dependence after 90 days but not to recurrent stroke, TIA or MI.

Measurement of the permittivity and loss of high-loss materials using a Near-Field Scanning Microwave Microscope.

In this paper improvements to a Near-Field Scanning Microwave Microscope (NSMM) are presented that allow the loss of high loss dielectric materials to be measured accurately at microwave frequencies. This is demonstrated by measuring polar liquids (loss tangent tanδ≈1) for which traceable data is available. The instrument described uses a wire probe that is electromagnetically coupled to a resonant cavity. An optical beam deflection system is incorporated within the instrument to allow contact mode between samples and the probe tip to be obtained. Liquids are contained in a measurement cell with a window of ultrathin glass. The calibration process for the microscope, which is based on image-charge electrostatic models, has been adapted to use the Laplacian 'complex frequency'. Measurements of the loss tangent of polar liquids that are consistent with reference data were obtained following calibration against single-crystal specimens that have very low loss.

Associations of chronic heart failure with outcome in acute ischaemic stroke patients who received systemic thrombolysis: analysis from VISTA.

BACKGROUND AND PURPOSE: There are concerns that systemic thrombolysis might not achieve clinically important outcome amongst chronic heart failure (CHF) patients with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on the outcome of acute stroke patients who received thrombolysis. METHODS: A non-randomized cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive. The association of outcome amongst CHF patients with thrombolysis treatment was described using the modified Rankin scale (mRS) distribution at day 90, stratified by the presence of atrial fibrillation. Dichotomized outcomes were considered as a secondary end-point. RESULTS: 5677 patients were identified, of whom 2366 (41.7%) received thombolysis. Five hundred and three (8.9%) patients had CHF, of whom 209 (41.6%) received thrombolysis. The presence of CHF was associated with a negative impact on overall stroke outcome [odds ratio (OR) 0.73 (95% confidence interval (CI) 0.62-0.87), P < 0.001]. However, thrombolysis treatment was associated with favourable functional outcome using ordinal mRS, irrespective of CHF status, after adjustment for age and baseline National Institutes of Health Stroke Scale [OR 1.44 (95% CI 1.04-2.01, P = 0.029) for CHF patients versus OR 1.50 (95% CI 1.36-1.66, P < 0.001) for non-CHF patients]. CHF patients had higher mortality at day 90 than non-CHF patients. There was no significant difference for recurrent stroke or symptomatic intracerebral haemorrhage within 7 days of the initial stroke between CHF and thrombolysis groups. CONCLUSIONS: Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of CHF status, compared with their untreated peers. Our findings should reassure clinicians considering systemic thrombolysis treatment in hyperacute ischaemic stroke patients with CHF.

Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA.

BACKGROUND AND PURPOSE: Ischaemic stroke patients with atrial fibrillation (AF) are at risk of early recurrent stroke (RS). However, antithrombotics commenced at the acute stage may exacerbate haemorrhagic transformation, provoking symptomatic intracerebral haemorrhage (SICH). The relevance of antithrombotics on the patterns and outcome of the cohort was investigated. METHODS: A non-randomized cohort analysis was conducted using data obtained from VISTA (Virtual International Stroke Trials Archive). The associations of antithrombotics with the modified Rankin Scale (mRS) outcome and the occurrence of RS and SICH (each as a combined end-point of fatal and non-fatal events) at 90 days for post-stroke patients with AF were described. Dichotomized outcomes were also considered as a secondary end-point (i.e. mortality and good outcome measure at 90 days). RESULTS: In all, 1644 patients were identified; 1462 (89%) received antithrombotics, 157 (10%) had RS and 50 (3%) sustained SICH by day 90. Combined antithrombotic therapy (i.e. anticoagulants and antiplatelets), 782 (48%), was associated with favourable outcome on ordinal mRS and a significantly lower risk of RS, SICH and mortality by day 90, compared with the no antithrombotics group. The relative risk of RS and SICH appeared highest in the first 2 days post-stroke before attenuating to become constant over time. CONCLUSIONS: The risks and benefits of antithrombotics in recent stroke patients with AF appear to track together. Early introduction of anticoagulants (2-3 days post-stroke), and to a lesser extent antiplatelet agents, was associated with substantially fewer RS events over the following weeks but with no excess risk of SICH. More evidence is required to guide clinicians on this issue.

Clinically important atrial arrhythmia and stroke risk: a UK-wide online survey among stroke physicians and cardiologists.

BACKGROUND: A recording of ≥30 s is required for diagnosis of paroxysmal atrial fibrillation (AF) when using ambulatory electrocardiography (ECG) monitoring. It is unclear if shorter runs of atrial arrhythmia are relevant with regard to stroke risk. AIM: To assess current management of patients with atrial arrhythmia of <30 s duration detected on ambulatory ECG. DESIGN: Online survey. METHODS: An online survey was sent to cardiologists and stroke physicians in the UK, via their national societies. RESULTS: A total of 205 clinicians responded to the survey (130 stroke physicians, 64 cardiologists, 11 other). Regarding diagnosis of AF, 87% of responders would accept a single 12-lead ECG. In contrast, only 45% would accept a single episode lasting <30 s detected on ambulatory monitoring. There was more agreement with regard to the decision to anticoagulate. When asked whether they would anticoagulate eight hypothetical patients with non-diagnostic paroxysms of AF, there was a mean agreement of responses of 78.6%, with up to 94.1% agreement for high-risk patients. There was a trend suggesting that stroke physicians were more likely to accept an atrial arrhythmia of <30 s as 'AF' than cardiology specialists [OR 1.63 (95% CI 0.88-3.01), P = 0.12]. CONCLUSIONS: There is a lack of consensus on the diagnosis and management of patients with brief runs of atrial arrhythmia detected on ambulatory ECG. Further research is needed to clarify the risk of stroke in this unique population of patients.

Impact of right-handedness on anaesthetic sensitivity, intra-operative awareness and postoperative mortality.

Anatomical, neurological and behavioural research has suggested differences between the brains of right- and non-right-handed individuals, including differences in brain structure, electroencephalogram patterns, explicit memory and sleep architecture. Some studies have also found decreased longevity in left-handed individuals. We therefore aimed to determine whether handedness independently affects the relationship between volatile anaesthetic concentration and the bispectral index, the incidence of definite or possible intra-operative awareness with explicit recall, or postoperative mortality. We studied 5585 patients in this secondary analysis of data collected in a multicentre clinical trial. There were 4992 (89.4%) right-handed and 593 (10.6%) non-right-handed patients. Handedness was not associated with (a) an alteration in anaesthetic sensitivity in terms of the relationship between the bispectral index and volatile anaesthetic concentration (estimated effect on the regression relationship -0.52 parallel shift; 95% CI -1.27 to 0.23, p = 0.17); (b) the incidence of intra-operative awareness with 26/4992 (0.52%) right-handed vs 1/593 (0.17%) non-right-handed (difference = 0.35%; 95% CI -0.45 to 0.63%; p = 0.35); or (c) postoperative mortality rates (90-day relative risk for non-right-handedness 1.19, 95% CI 0.76-1.86; p = 0.45). Thus, no change in anaesthetic management is indicated for non-right-handed patients.

Allopurinol reduces brachial and central blood pressure, and carotid intima-media thickness progression after ischaemic stroke and transient ischaemic attack: a randomised controlled trial.

OBJECTIVE: Central blood pressure (CBP) and carotid intima-media thickness (CIMT) are surrogate measures of cardiovascular risk. Allopurinol reduces serum uric acid and oxidative stress and improves endothelial function and may therefore reduce CBP and CIMT progression. This study sought to ascertain whether allopurinol reduces CBP, arterial stiffness and CIMT progression in patients with ischaemic stroke or transient ischaemic attack (TIA). METHODS: We performed a randomised, double-blind, placebo-controlled study, examining the effect of 1-year treatment with allopurinol (300 mg daily), on change in CBP, arterial stiffness and CIMT progression at 1 year and change in endothelial function and circulating inflammatory markers at 6 months. Patients aged over 18 years with recent ischaemic stroke or TIA were eligible. RESULTS: Eighty participants were recruited, mean age 67.8 years (SD 9.4). Systolic CBP [-6.6 mm Hg (95% CI -13.0 to -0.3), p=0.042] and augmentation index [-4.4% (95% CI -7.9 to -1.0), p=0.013] were each lower following allopurinol treatment compared with placebo at 12 months. Progression in mean common CIMT at 1 year was less in allopurinol-treated patients compared with placebo [between-group difference [-0.097 mm (95% CI -0.175 to -0.019), p=0.015]. No difference was observed for measures of endothelial function. CONCLUSIONS: Allopurinol lowered CBP and reduced CIMT progression at 1 year compared with placebo in patients with recent ischaemic stroke and TIA. This extends the evidence of sustained beneficial effects of allopurinol to these prognostically significant outcomes and to the stroke population, highlighting the potential for reduction in cardiovascular events with this treatment strategy. TRIAL REGISTRATION NUMBER: ISRCTN11970568.

Interdependence of stroke outcome scales: reliable estimates from the Virtual International Stroke Trials Archive (VISTA).

BACKGROUND AND PURPOSE: Clinical deficits from stroke are diverse, prompting measurement in trials by a range of outcome scales. Statistical and clinical advantage can be gained by combining scales into a global outcome provided combinations are chosen with limited correlations. We aimed to clarify the interdependence of outcome scales by systematic review of published data and by novel analysis of data from completed acute trials. SUMMARY OF REVIEW: We systematically searched ScienceDirect and PubMed to summarize published data on correlations between stroke outcome scales. We generated new data on correlations among salient scales at 90 days poststroke in patients from the Virtual International Stroke Trials Archive (VISTA). We calculated Pearson and Spearman-Rank correlation coefficients for continuous and ordinal measures, respectively. We also assessed partial correlations, adjusted for baseline National Institute of Health Stroke Scale (NIHSS), and age. Published estimates of interdependence were limited to small single-trial cohorts and gave divergent results. From the more extensive VISTA dataset, we found that the modified Rankin Scale at 90 days poststroke explained 80.8% of the National Institute of Health Stroke Scale at 90 days poststroke and 86.5% of the European Stroke Scale. National Institute of Health Stroke Scale explained 75.9% of the Barthel Index and 81.2% of the Scandinavian Stroke Scale. After adjustment, modified Rankin Scale explained 56.6% of National Institute of Health Stroke Scale, 75.2% of Barthel Index. National Institute of Health Stroke Scale explained 60.2% of Barthel Index. CONCLUSION: Correlations and partial correlations among stroke outcome scales in trial datasets are higher than previously reported. The new estimates are more reliable for trial planning due to the sample size and diversity.

A survey of principal researchers who lead research into Adults with Incapacity in Scotland.

BACKGROUND: Scotland's 'A' Research Ethics Committee (SAREC, previously MREC A) has exclusive authority to consider research involving Adults with Incapacity in Scotland. No appeal facility exists although resubmissions are accepted. Legislation covering research in England and Wales has created anomalies. RECs 'recognised' by the UK Ethics Committee (3 in Scotland, several in England) can approve drug studies involving Adults with Incapacity in Scotland. Several English RECs can approve studies led from outside Scotland. METHODS: We conducted an anonymous online survey of researchers experienced in studies involving Adults with Incapacity to establish their opinions on the role of SAREC. The survey had 5 multiple-choice questions. Two questions invited a free-text comment. RESULTS: Seventy-seven researchers (45% response) completed the survey. The majority (61/76, 80%) received a favourable opinion from SAREC immediately/after minor revision. The consensus was a single, experienced committee is advantageous to researchers (69/77 (90%)) and research participants (65/75 (87%)). There was no association between application outcome and opinion on whether a single committee is advantageous for researchers (p = 0.39 (Fisher's exact test)) or research participants (p = 0.49). Most (42/76, 55%) favoured the current system for reviewing decisions. CONCLUSIONS: The research establishment favours retaining expertise in one committee. Most are content not having an external appeal facility.

Preoperative risk factors in 10 418 patients with prior myocardial infarction and 5241 patients with prior unstable angina undergoing elective coronary artery bypass graft surgery.

BACKGROUND: The EuroSCORE associates coronary artery bypass graft (CABG) surgery with higher perioperative risk in the first 3 months after a myocardial infarction (MI). The optimal scheduling of CABG surgery after unstable angina (UA) is unknown. We investigated the preoperative predictors of adverse outcomes in patients undergoing CABG with prior MI or UA and investigated the importance of time interval between the cardiac event and CABG. METHODS: The Hospital Episode Statistics database (April 2006-March 2010) was analysed for elective admissions for CABG. Independent preoperative patient factors influencing length of stay, readmission rates, and mortality, were identified by logistic regression and presented as adjusted odds ratios (ORs). RESULTS: A total of 10 418 patients with prior MI (mortality 1.8%) and 5241 patients with prior UA (mortality 2.2%) were included in the respective cohorts. Multiple risk factors were identified in each population including liver disease and renal failure. The time interval from cardiac event (MI or UA) to elective CABG surgery did not influence perioperative outcomes when analysed as a continuous measure or using the arbitrary 3-month threshold [MI, OR 1.1 (0.78-1.57) and UA, OR 0.65 (0.39-1.09)]. CONCLUSIONS: Our hypothesis generating data suggest that the increased risk currently allocated in the EuroSCORE for an interval of 3 months between MI and CABG should be critically re-evaluated. Furthermore, prior MI should not be discounted as a risk factor if it is more than 3 months old.