Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

Campbell, B. C. V. et al. (2018) Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurology, 17(1), pp. 47-53. (doi:10.1016/S1474-4422(17)30407-6) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/149670/ variables. An alternative approach using propensity-score stratification was also used. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Bias was assessed using the Cochrane tool.Findings: Of 1764 patients in 7 trials, 871 were allocated to endovascular thrombectomy. After exclusion of 74 patients (72 who did not undergo the procedure and 2 with missing data on anaesthetic strategy), 236/797 (30%) of endovascular patients were treated under GA. At baseline, GA patients were younger and had shorter time to randomisation but similar pre-treatment clinical severity compared to non-GA. Endovascular thrombectomy improved functional outcome at 3 months versus standard care in both GA (adjusted common odds ratio (cOR) 1·52, 95%CI 1·09-2·11, p=0·014) and non-GA (adjusted cOR 2·33, 95%CI 1·75-3·10, p<0·001) patients. However, outcomes were significantly better for those treated under non-GA versus GA (covariate-adjusted cOR 1·53, 95%CI 1·14-2·04, p=0·004; propensitystratified cOR 1·44 95%CI 1·08-1·92, p=0·012). The risk of bias and variability among studies was assessed to be low.Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. Funding:The HERMES collaboration was funded by an unrestricted grant from Medtronic to the University of Calgary. Research in contextEvidence before this study between abolition of the thrombectomy treatment effect in MR CLEAN and no effect in THRACE. Three single-centre randomised trials of general anaesthesia versus conscious sedation found either no difference in functional outcome between groups or a slight benefit of general anaesthesia. Added value of this studyThese data from contemporary, high quality randomised trials form the largest study to date of the association between general anesthesia and the benefit of endovascular thrombectomy versus standard care. We used two different approaches to adjust for baseline imbalances (multivariable logistic regression and propensity-score stratification). We found that GA for endovascular thrombectomy, as practiced in contemporary clinical care across a wide range of expert centres during the rand...

In contrast, coadministration of 0.3 g/kg i.v. L-768673 ϩ 1.0 g/kg i.v. timolol suppressed the induction of VT by PVS (8/10, 80% rendered noninducible versus 1/10, 10% noninducible in vehicle group; p Ͻ 0.01) and prevented the development of acute ischemic lethal arrhythmias (3/10, 30% incidence versus 8/10, 80% incidence in vehicle group; p Ͻ 0.05). Concomitant administration of low-dose L-768673 ϩ timolol produced modest increases in QTc and paced QT intervals (4.5 Ϯ 1.2 and 5.5 Ϯ 1.4%; both p Ͻ 0.01), increases in noninfarct zone relative and effective refractory periods (7.0 Ϯ 1.7 and 12.3 Ϯ 3.0%; both p Ͻ 0.01), and lesser increases in infarct zone relative and effective refractory periods (5.3 Ϯ 1.6 and 5.8 Ϯ 1.4%; both p Ͻ 0.01). These findings suggest that concomitant low-dose I Ks and ␤-adrenergic blockade may constitute a potential pharmacologic strategy for prevention of malignant ischemic ventricular arrhythmias.Delay of myocardial repolarization (class III electrophysiologic activity) via blockade of repolarizing potassium currents has been advanced as a potential antiarrhythmic mechanism. This is based on the premise that sufficient prolongation of myocardial refractoriness results in a wavelength of excitation that exceeds the path length of reentrant circuits, thereby preventing the initiation and/or maintenance of reentrant rhythms (Wellens et al., 1984). Myocardial repolarization in the majority of mammalian species studied, including humans, is controlled mainly by the interplay of the rapidly (I Kr ) and slowly (I Ks ) activating, delayed rectifier potassium currents (Sanguinetti and Jurkiewicz, 1990;Wang et al., 1994;Liu and Antzelevitch, 1995;Li et al., 1996;Salata et al., 1996a;Virag et al., 2001). The clinical assessment of selective blockers of I Kr for the treatment of malignant ventricular arrhythmia has yielded disappointing results. d-Sotalol increased mortality in patients with previous myocardial infarction and left ventricular dysfunction (Waldo et al., 1996), and dofetilide displayed a neutral effect on mortality in patients with reduced left ventricular function and congestive heart failure (Torp-Pedersen et al., 1999). Characteristics of I Kr blockers, which have been proposed to limit clinical antiarrhythmic efficacy, include reverse frequency dependence, whereby class III activity is diminished at faster heart rates and exaggerated at slower rates (Nattel and Zeng, 1984;Hondeghem and Snyders, 1990), and reduction of class III activity in the setting of sympathetic stimulation (Sanguinetti et al., 1991;Schreieck et al., 1997).A number of structurally distinct selective I Ks blockers recently have become available for preclinical assessment. Initial studies indicate that selective I Ks block may provide a profile of class III action differing significantly from that of I Kr block, particularly with regard to frequency dependence

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Granular pesticide carriers that possess high quality attributes are needed. Some of the main considerations with which pesticide formulators and users contend include physical durability, flowability, ballistics properties, chemical compatibility, favorable econometrics, and pesticidal efficacy. An evaluation of the commercially available mined and recycled materials, as well as an analysis of the requirements for efficacious granules, has led the researchers to define a combination of criteria that was previously unrealized in any of the selections of the then commercially available granular pesticide carriers. The research objective that emerged, developing a more optimal pesticide granule, was defined by these criteria. Many dozens of prototype formulations were produced in a laboratory granulation system and were evaluated by various physical test methods until the original design criteria were met. Subsequently, a period of field efficacy trials took place in which suitability for particular active ingredients, target pests, and cultural conditions was determined. An engineered composite granule and production process was developed during the course of this research. The resulting granules have a unique combination of characteristics: robust enough to withstand the physical stresses of bulk handling, formulating and field application, good flowability and compositional characteristics, plus a unique degree of dispersion upon the application of a small amount of moisture over the treated area after the granules have been applied. This post-application water dispersion mechanism appears to allow enhanced pesticidal efficacy for soil treatment and systemic active ingredients, and has demonstrated numerous aesthetic and hazard reduction attributes of interest. The resulting material has competitive economics, and has been patented and trademarked as DG Lite®.