1.
Beta-Blockade in Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-Analysis
Ramesh AV, Banks CFK, Mounstephen PE, Crewdson K, Thomas M
Neurocritical care. 2020
Abstract
BACKGROUND/OBJECTIVE Sympathetic nervous system activation after aneurysmal subarachnoid hemorrhage (aSAH) is associated with complications and poor outcome. In this systematic review and meta-analysis, we investigate the effect of beta-blockers on outcome after aSAH. METHODS The review was prospectively registered with PROSPERO (CRD42019111784). We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, published conference proceedings, and abstracts. Eligible studies included both randomized controlled trials and observational studies up to October 2018, reporting the effect of beta-blocker therapy on the following outcomes in aSAH: mortality, vasospasm, delayed cerebral ischemia, infarction or stroke, cardiac dysfunction, and functional outcomes. Studies involving traumatic SAH were excluded. Citations were reviewed, and data extracted independently by two investigators using a standardized proforma. RESULTS We identified 819 records with 16 studies (four were randomized controlled trials) including 6702 patients selected for analysis. Exposure to beta-blockade either before or after aSAH was associated with a significant reduction in unadjusted mortality (RR 0.63, 95% CI 0.42-0.93, p = 0.02). A significant reduction in unadjusted mortality was also seen in prospective trials of post-event beta-blockade (RR 0.51, 95% CI 0.28-0.93, p = 0.03). Statistically significant differences were not seen for other outcomes investigated. CONCLUSIONS In adult patients with aSAH, beta-blocker therapy is associated with a mortality benefit. Studies are generally of a low quality with considerable clinical heterogeneity. Prospective large interventional trials with patient centered outcomes are required to validate this finding.
2.
Darbepoetin alfa once monthly corrects anaemia in patients with chronic kidney disease not on dialysis
Roger SD, Kolmakova E, Fung M, Malecki R, Vinhas J, Dellanna F, Thomas M, Manamley N, Ferenczi S
Nephrology. 2014;19((5):):266-74.
Abstract
AIM: While darbepoetin alfa (DA) can be administered once monthly (QM) to maintain haemoglobin (Hb) concentrations in anaemic patients with chronic kidney disease not on dialysis (CKD-ND), the QM use of DA for anaemia correction has not been previously investigated. METHODS In this randomized, double-blind, non-inferiority, active-controlled study, adult subjects with CKD-ND, Hb levels <10g/dL, and not treated with an erythropoiesis-stimulating agent were randomized 1:1 to receive DA every 2 weeks (Q2W) or QM for 33 weeks with initial doses of 0.75mug/kg Q2W or 1.5mug/kg QM. Subjects were treated to target Hb levels of 10-12g/dL and >1g/dL increase from baseline. The primary end-point was Hb change between baseline and the evaluation period (weeks 29-33), with a non-inferiority margin of -0.5g/dL. RESULTS Three hundred and fifty-five subjects received >1 dose of DA. Mean (95% confidence interval [CI]) change in Hb between baseline and the evaluation period was 2.16 (1.98-2.33) g/dL for the Q2W group and 1.97 (1.80-2.14) g/dL for the QM group, the mean (95% CI) difference in Hb change being -0.19 (-0.43 to 0.05) g/dL. Most subjects (97.9% Q2W; 98.1% QM) achieved a Hb level >10.0g/dL and >1.0g/dL increase in Hb from baseline. Mean DA (SD) weekly equivalent doses over the evaluation period were 0.20 (0.23) and 0.27 (0.31) mug/kg per week for the Q2W and QM groups, respectively. Safety profiles were similar between groups. CONCLUSION In subjects with CKD-ND, QM dosing was non-inferior to Q2W dosing for anaemia correction and had a similar safety profile. 2014 Asian Pacific Society of Nephrology.