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.

BackgroundThe increasing availability and diversity of omics data in the post-genomic era offers new perspectives in most areas of biomedical research. Graph-based biological networks models capture the topology of the functional relationships between molecular entities such as gene, protein and small compounds and provide a suitable framework for integrating and analyzing omics-data. The development of software tools capable of integrating data from different sources and to provide flexible methods to reconstruct, represent and analyze topological networks is an active field of research in bioinformatics.ResultsBisoGenet is a multi-tier application for visualization and analysis of biomolecular relationships. The system consists of three tiers. In the data tier, an in-house database stores genomics information, protein-protein interactions, protein-DNA interactions, gene ontology and metabolic pathways. In the middle tier, a global network is created at server startup, representing the whole data on bioentities and their relationships retrieved from the database. The client tier is a Cytoscape plugin, which manages user input, communication with the Web Service, visualization and analysis of the resulting network.ConclusionBisoGenet is able to build and visualize biological networks in a fast and user-friendly manner. A feature of Bisogenet is the possibility to include coding relations to distinguish between genes and their products. This feature could be instrumental to achieve a finer grain representation of the bioentities and their relationships. The client application includes network analysis tools and interactive network expansion capabilities. In addition, an option is provided to allow other networks to be converted to BisoGenet. This feature facilitates the integration of our software with other tools available in the Cytoscape platform. BisoGenet is available at http://bio.cigb.edu.cu/bisogenet-cytoscape/.

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...

BackgroundUnder-representation of some socio-economic groups in medicine is rooted in under-representation of those groups in applications to medical school. This study aimed to explore what may deter school-age children from applying to study medicine.MethodsWorkshops were undertaken with school students aged 16–17 years (‘Year 12’, n = 122 across three workshops) and 13–14 years (‘Year 9’, n = 295 across three workshops). Workshops used a variety of methods to identify and discuss participants’ perceptions of medicine, medical school and the application process. Year 12 workshops focused on applications and medical school, while Year 9 took a broader approach reflecting their relative distance from applying. Subsequent workshops were informed by the findings of earlier ones.ResultsThe main finding was that potential applicants had limited knowledge about medicine and medical school in several areas. Older students would benefit from accessible information about medical degrees and application processes, access to work experience opportunities and personal contact with medical students and junior doctors, particularly those from a similar background. Younger students demonstrated a lack of awareness of the breadth of medical careers and a limited understanding of what medicine encompasses. Many Year 9 students were attracted by elements of practice which they did not associate with medicine, such as ‘talking to people with mental health problems’. An exercise addressing this elicited an increase in their interest in medicine.These issues were identified by participants as being more marked for those without knowledgeable support at home or school. It was apparent that school teachers may not be equipped to fill these knowledge gaps.ConclusionGaps in knowledge and support may reflect the importance of ‘social capital’ in facilitating access to medical school. Medical schools could act as hubs to introduce students to resources which are essential for widening participation. Outreach and support to schools may ensure that fundamental knowledge gaps are equitably addressed for all prospective applicants.More generally, a focus on medicine which under-emphasises aspects of medical practice involving communication may deter some students and have longer term impact on recruitment to careers including general practice and psychiatry.

Background: Early neurological deterioration (END) following acute stroke is associated with poorer long-term outcomes. Identification of patients at risk could assist early monitoring and treatment decisions. This review summarised the evidence describing non-radiological biomarkers for END. Summary: Electronic searches from January 1990 to March 2017 identified studies reporting a blood/cerebrospinal fluid (CSF)/urine biomarker measurement within 24 h of acute stroke and at least 2 serial assessments of clinical neurological status (< 24 h and < 7 days). Out of 12,895 citations, 82 studies were included, mostly focusing on ischaemic stroke. Using higher neurological thresholds, the n-weighted END incidence for ischaemic stroke was 11.9% (95% CI 11.4–12.4%) and 18.6% (17.9–19.2%) for lower thresholds. Incidence decreased with advancing study publication year (Pearson r-squared 0.23 and 0.15 for higher and lower threshold studies). After classification into 3 broad categories, meta-analysis showed that biomarkers associated with increased END risk (n; fixed-effects mean difference; 95% CI) were “metabolic” (glucose [n = 9,481; 0.90 mmol/L; 0.74–1.06], glycosylated haemoglobin [n = 3,146; 0.33%; 0.19–0.46], low-density lipoprotein [n = 4,839; 0.13 mmol/L; 0.06–0.21], total cholesterol [n = 4,762; 0.21 mmol/L; 0.11–0.31], triglycerides [n = 4,820; 0.11 mmol/L; 0.06–0.17], urea [n = 1,351; 0.55 mmol/L; 0.14–0.96], decreasing albumin [n = 513; 0.33 g/dL; 0.05–0.61]); “inflammatory and excitotoxic” (plasma glutamate [n = 688; 60.13 µmol/L; 50.04–70.22], CSF glutamate [n = 369; 7.50 µmol/L; 6.76–8.23], homocysteine [n = 824; 2.15 µmol/L; 0.68–3.61], leucocytes [n = 3,766; 0.54 × 10⁹/L; 0.34–0.74], high-sensitivity C-reactive protein [n = 1,707; 3.79 mg/L; 1.23–6.35]); and “coagulation/haematological” (fibrinogen [n = 3,132; 0.32 g/L; 0.25–0.40]; decreasing haemoglobin [n = 3,586; 2.38 g/L; 0.15–4.60]). Key Messages: Declining incidence of END may represent improving care standards; however, it remains a frequent occurrence. Although statistical associations exist between biomarkers and an increased risk of END, the most promising still need prospective evaluation to determine their additional value relative to baseline radiological and clinical characteristics.