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...

Background: Stroke is one of the most disabling neurological conditions. Clinical research is vital for expanding knowledge of treatment effectiveness among stroke patients. However, evidence begins to accumulate that stroke patients who take part in research represent only a small proportion of all stroke patients. Research participants may also differ from the broader patient population in ways that could potentially distort treatment effects reported in therapeutic trials. The aims of this study were to estimate the proportion of stroke patients who take part in clinical research studies and to compare demographic and clinical profiles of research participants and non-participants. Methods: 5,235 consecutive patients admitted to the Stroke Care Unit of the Royal Melbourne Hospital, Melbourne, Australia, for stroke or transient ischaemic attack between January 2004 and December 2011 were studied. The study used cross-sectional design. Information was collected on patients' demographic and socio-economic characteristics, risk factors, and comorbidities. Associations between research participation and patient characteristics were initially assessed using χ² or Mann-Whitney tests, followed by a multivariable logistic regression analysis. The logistic regression analysis was carried out using generalised estimating equations approach, to account for patient readmissions during the study period. Results: 558 Stroke Care Unit patients (10.7%) took part in at least one of the 33 clinical research studies during the study period. Transfer from another hospital (OR = 0.35, 95% CI 0.22-0.55), worse premorbid function (OR = 0.61, 95% CI 0.54-0.70), being single (OR = 0.61, 95% CI 0.44-0.84) or widowed (OR = 0.77, 95% CI 0.60-0.99), non-English language (OR = 0.67, 95% CI 0.53-0.85), high socio-economic status (OR = 0.74, 95% CI 0.59-0.93), residence outside Melbourne (OR = 0.75, 95% CI 0.60-0.95), weekend admission (OR = 0.78, 95% CI 0.64-0.94), and a history of atrial fibrillation (OR = 0.79, 95% CI 0.63-0.99) were associated with lower odds of research participation. A history of hypertension (OR = 1.50, 95% CI 1.08-2.07) and current smoking (OR = 1.23, 95% CI 1.01-1.50) on the other hand were associated with higher odds of research participation. Conclusions: The results of this study indicate that stroke patients who take part in clinical research do not represent ‘typical' patient admitted to a stroke unit. The imbalance of prognostic factors between stroke participants and non-participants has serious implications for interpretation of research findings reported in stroke literature. This study provides insights into clinical, demographic, and socio-economic characteristics of stroke patients that could potentially be targeted to enhance generalizability of stroke research studies. Given the imbalance of prognostic factors between research participants and non-participants, future studies need to examine differences in stroke outcomes of these groups of patients.

IMPORTANCEElevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs in firefighting foams and have previously been shown to have higher PFAS levels in blood samples than the general population. No interventions have been shown to reduce PFAS levels. OBJECTIVE To examine the effect of blood or plasma donations on PFAS levels in firefighters in Australia. DESIGN, SETTING, AND PARTICIPANTS This 52-week, open-label, randomized clinical trial enrolled participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff orcontractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were able to provide written informed consent. Analysis was performed on an intention-to-treat basis from May to July 2021. INTERVENTIONSFirefighters with baseline PFOS levels of 5 ng/mL or more were randomly assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months, or be observed only. MAIN OUTCOMES AND MEASURESThe primary end points were changes in the serum PFOS and perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after observation only. Secondary end points included changes in serum PFAS levels from week 52 to week 64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function, and lipid profile from screening to week 52. RESULTSA total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood, and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was significantly reduced by plasma donation (-2.9 ng/mL; 95% CI, -3.6 to -2.3 ng/mL; P < .001) and blood donation (-1.1 ng/mL; 95% CI, -1.5 to -0.7 ng/mL; P < .001) but was unchanged in the observation group. The mean level of PFHxS was significantly reduced by plasma donation (-1.1 ng/mL; 95% CI, -1.6 to -0.7 ng/mL; P < .001), but no significant change was observed in the blood donation or observation groups. Analysis between groups indicated that plasma donation had a larger treatment effect than blood donation, but both were significantly more efficacious than observation in reducing PFAS levels. (continued) Key Points Question Can levels of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the blood be reduced by blood or plasma donations? Findings In this randomized clinical trial of 285 firefighters, both blood and plasma donations resulted in significantly lower PFAS levels than observation alone. Plasma donation was the most effective intervention, reducing mean serum perfluorooctane sulfonate levels by 2.9 ng/mL compared with a 1.1-ng/mL reduction with blood donation, a significant difference; similar changes were seen with other PFASs. Meaning Blood or pl...

IntroductionPerfluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of compounds that have been used in hundreds of industrial applications and consumer products including aqueous film-forming foam (AFFF) for many years. Multiple national and international health and environmental agencies have accepted that PFAS exposures are associated with numerous adverse health effects. Australian firefighters have been shown to have elevated levels of PFAS in their blood, specifically perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), due to the historical use of AFFF. While PFAS concentrations decline over time once the source of exposure has been removed, their potential adverse health effects are such that it would be prudent to develop an intervention to lower levels at a faster rate than occurs via natural elimination rates.Methods and analysisThis is a randomised controlled trial of current and former Australian firefighters in the Metropolitan Fire Brigade/Fire Rescue Victoria, and contractors, with previous occupational exposure to PFAS and baseline elevated PFOS levels. The study is investigating whether whole blood donation every 12 weeks or plasma donation every 6 weeks will significantly reduce PFAS levels, compared with a control group. We have used covariate-adaptive randomisation to balance participants’ sex and blood PFAS levels between the three groups and would consider a 25% reduction in serum PFOS and PFHxS levels to be potentially clinically significant after 12 months of whole blood or plasma donation. A secondary analysis of health biomarkers is being made of changes between screening and week 52 in all three groups.Ethics and disseminationThis trial has been approved by Macquarie University Human Research Ethics Committee (reference number: 3855), final protocol V.2 dated 12 June 2019. Study results will be disseminated via peer-reviewed publications and presentations at conferences.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000204145).