Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

IV immunoglobulin in patients with myasthenia gravis A randomized controlled trial

Abstract: Objective: We aimed to determine the effectiveness of IV immunoglobulin (IVIG) in the treatment of patients with myasthenia gravis (MG) and worsening weakness in a randomized, placebo-controlled, masked study. Methods: Fifty-one patients with worsening weakness due to MG were randomized to infusion with 2 g/kg of IVIG or an equivalent volume of IV dextrose 5% in water. The Quantitative Myasthenia Gravis (QMG) Score for Disease Severity, a validated clinical composite scale, was calculated by a masked observer at baseline and days 14 and 28. Results: In IVIG-treated patients, a clinically meaningful improvement in QMG Score for Disease Severity was observed at day 14 and persisted at day 28. The greatest improvement occurred in patients with more severe disease as defined by a QMG Score for Disease Severity greater than 10.5. Conclusion: This study provides level 1 evidence for the effectiveness of IV immunoglobulin in patients with worsening weakness due to myasthenia gravis.

Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study

Abstract: PURPOSE: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.METHODS: The large observational st ...

Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons.

Abstract: Propofol (2,6 di-isopropylphenol) is an alkyphenol recently introduced for use as a general anesthetic. The modulation of GABAA receptor activation and desensitization by propofol was studied using a rapid perfusion system and whole-cell voltage-clamp recordings from mouse hippocampal neurons. The effects of concentrations of propofol used clinically on single-channel and synaptic currents were also examined. Propofol evoked current responses (EC50 = 61 microM) and shifted the dose-response curve of GABA-activated current to the left without altering the maximum of the GABA response. Preincubation with propofol and GABA led to desensitization of the GABA response (EC50 = 454 microM and 23 microM, respectively). Saturating concentrations of GABA (600 microM) evoked currents that peaked and then declined in a biexponential fashion with fast and slow time constants of tau f = 1.0 sec and tau s = 3.5 sec. Propofol (10 microM) did not change the amplitude of the peak response but decreased the rates of decay approximately 1.5-fold and enhanced the steady-state current proportionately. Recovery from desensitization was also biexponential (tau f = 11 sec, tau s = 69 sec) but not influenced by propofol. Single-channel recordings from outside-out patches demonstrated that both propofol and GABA activated channels with a 30 pS and 21 pS open state. Propofol increased the frequency but not the duration or conductance of GABA-activated events. Miniature inhibitory postsynaptic currents (mlPSCs) were evoked by the application of hypertonic sucrose to the cell soma. Propofol (2 microM) prolonged the decay time of mlPSCs to an extent similar to which it increased the open probability of GABA-activated channels (2.3- vs 3-fold). A sequential model, based on a previous scheme of GABA receptor gating (Weiss and Magelby, 1989), is presented to summarize propofol's actions on GABAA receptor function. We show through simulation that the model reliably reproduced the whole-cell tracings. Our results indicate that propofol's neurodepressive actions will be associated with enhancement of inhibitory synaptic transmission.

The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: A simulation study

Abstract: Meta-analysis of continuous outcomes traditionally uses mean difference (MD) or standardized mean difference (SMD; mean difference in pooled standard deviation (SD) units). We recently used an alternative ratio of mean values (RoM) method, calculating RoM for each study and estimating its variance by the delta method. SMD and RoM allow pooling of outcomes expressed in different units and comparisons of effect sizes across interventions, but RoM interpretation does not require knowledge of the pooled SD, a quantity generally unknown to clinicians. To evaluate performance characteristics of MD, SMD and RoM using simulated data sets and representative parameters. MD was relatively bias-free. SMD exhibited bias (~5%) towards no effect in scenarios with few patients per trial (n = 10). RoM was bias-free except for some scenarios with broad distributions (SD 70% of mean value) and medium-to-large effect sizes (0.5–0.8 pooled SD units), for which bias ranged from -4 to 2% (negative sign denotes bias towards no effect). Coverage was as expected for all effect measures in all scenarios with minimal bias. RoM scenarios with bias towards no effect exceeding 1.5% demonstrated lower coverage of the 95% confidence interval than MD (89–92% vs. 92–94%). Statistical power was similar. Compared to MD, simulated heterogeneity estimates for SMD and RoM were lower in scenarios with bias because of decreased weighting of extreme values. Otherwise, heterogeneity was similar among methods. Simulation suggests that RoM exhibits comparable performance characteristics to MD and SMD. Favourable statistical properties and potentially simplified clinical interpretation justify the ratio of means method as an option for pooling continuous outcomes.

Donepezil preserves cognition and global function in patients with severe Alzheimer disease

Abstract: Objective: To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD). Methods: Patients with severe AD (Mini-Mental State Examination [MMSE] scores 1 to 12 and Functional Assessment Staging [FAST] scores ≥6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinician9s Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving ≥1 dose of donepezil or placebo. Results: Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD. Conclusion: Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.