METHODS: 10 010 high-risk noncardiac surgical patients were randomized aspirin or placebo and clonidine or placebo. Neuraxial block was defined as intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia. Postoperative epidural analgesia was defined as postoperative epidural local anaesthetic and/or opioid administration. We used logistic regression with weighting using estimated propensity scores.
RESULTS: Neuraxial block was not associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI (confidence interval), 0.73-1.08; P=0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI, 0.53-1.35; P=0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74-1.12; P=0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44-2.49; P=0.91). Neuraxial block was associated with less clinically important hypotension (39% vs 46%; OR, 0.90; 95% CI, 0.81-1.00; P=0.04). Postoperative epidural analgesia was not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89-2.48; P=0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35-1.99; P=0.68], myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90-2.61; P=0.11], stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18-2.32; P=0.50] or clinically important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95-2.09; P=0.09).
CONCLUSIONS: Neuraxial block and postoperative epidural analgesia were not associated with adverse cardiovascular outcomes among POISE-2 subjects.
METHODS: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.
RESULTS: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.
CONCLUSION: We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.