A stepped-wedge cluster-randomized trial to improve adherence to evidence-based practices for acute stroke management

Background There is limited evidence regarding the optimal design and composition of multifaceted quality improvement programs to improve acute stroke care. The researchers aimed to test the effectiveness of a co-designed multifaceted intervention (STELAR: Shared Team Efforts Leading to Adherence Results) directed at hospital clinicians for improving acute stroke care tailored to the local context using feedback of national registry indicator data. Methods STELAR was a stepped-wedge cluster trial (partial randomization) using routinely collected Australian Stroke Clinical Registry data from Victorian hospitals segmented in two-month blocks. Each hospital (cluster) contributed control data from May 2017 and data for the intervention phase from July 2017 until September 2018. The intervention was multifaceted, delivered predominantly in two educational outreach workshops by experienced, external improvement facilitators, consisting of (1) feedback of registry data to identify practice gaps and (2) interprofessional education, barrier assessment, and documentation of an agreed action plan initiated by local clinical leaders appointed as change champions for prioritized clinical indicators. The researchers provided additional outreach support by e-mail/telephone for two months. Multilevel, multivariable regression models were used to assess change in a composite outcome of indicators selected for actions plans (primary outcome) and individual indicators (secondary outcome). Patient survival and disability 90–180 days after stroke were also compared. Results Nine hospitals (clusters) participated, and 144 clinicians attended 18 intervention workshops. The control phase included 1,001 patients (median age 76.7 years; 47.4% female, 64.7% ischemic stroke), and the intervention phase 2,146 patients (median age 74.9 years; 44.2% female, 73.8% ischemic stroke). Compared to the control phase, the median score for the composite outcome for the intervention phase was 17% greater for the indicators included in the hospitals’ action plans (range 3% to 30%, p = 0.016) and overall for the 10 indicators 6% greater (range 3% to 10%, p < 0.001). Compared to the control phase, patients in the intervention phase more often received stroke unit care (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.05–1.84), were discharged on antithrombotic medications (OR 1.87, 95% CI 1.50–2.33), and received a discharge care plan (OR 1.27, 95% CI 1.05–1.53). Patient outcomes were unchanged. Conclusion External quality improvement facilitation using workshops and remote support, aligned with routine monitoring via registries, can improve acute stroke care

NMR Study of General Anesthetic Interaction with nAChR β2 Subunit☆

The molecular basis of anesthetic interaction with membrane proteins has been explored via determination of anesthetic effects on the structure and dynamics of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) β2 subunit in dodecylphosphocholine (DPC) micelles by 1H and 15N solution-state NMR. Both 1-chloro-1,2,2-trifluorocyclobutane (F3) and isoflurane, two volatile general anesthetics, induced nonuniform changes in chemical shifts among residues in TM2e. Saturation transfer difference NMR experiments further confirmed the direct anesthetic interaction with TM2e. A significant and more specific anesthetic interaction was observed on three leucine residues at the helix C-terminus. Although the TM2e helical structure remained after addition of anesthetics, plausible shortening and lengthening of helix hydrogen bonds were evidenced by periodic changes in backbone amide chemical shifts. The TM2e backbone dynamics were determined on the basis of the 15N relaxation rate constants, R1 and R2, and the 15N-[1H] NOE using the model-free approach. The global tumbling time (11.7 ns) of TM2e in micelles slightly increased (∼12.3–12.5 ns) in the presence of anesthetics. The order parameter, S2, exceeded 0.9 for all 15N-labeled residues, showing a restricted internal motion. Anesthetics appear to have minor effect on the TM2e's internal motion. This study provided the basis for subsequent more comprehensive studies of anesthetic effects on the transmembrane domain complex of neuronal nAChR