Study objective:The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, activecontrolled, multicenter trial of methoxyflurane in the emergency setting in Europe.Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score !4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2Â3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief.Results: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. Conclusion:These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain.

There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug. After univariate analysis, donor age, duration of hospital stay, and creatinine clearance (third month) showed significant differences between rejecters and nonrejecters. In addition, mean tacrolimus trough concentrations on day 5, day 7, mean of days 1-7, and mean of days 5-7 were found to be significantly lower in rejecters (P = 0.009, P = 0.012, P = 0.006, and P = 0.035, respectively). Receiver operating characteristic curve analysis with tacrolimus trough concentrations measured on days 5 and 7 was able to discriminate between patients with and without acute rejection (P = 0.028 and P = 0.048 after Bonferroni correction). The tacrolimus trough concentration with the best sensitivity-specificity balance was 9.3 ng/mL on day 5 and 8.7 ng/mL on day 7. In the Kaplan-Meier analysis, patients with tacrolimus trough concentrations below 9.3 mg/mL on day 5 showed a lower survival time without acute rejection (P = 0.048 after correction) in comparison with patients with tacrolimus trough concentrations above this concentration. After logistic regression, we obtained a model relating rejection with sex, donor age, and tacrolimus trough concentrations on day 5 (P = 0.004). No significant relationship between tacrolimus trough concentrations and delta creatinine clearance from week 1 to month 3 was obtained. These results confirm that tacrolimus trough concentrations during the first week are an important predictor of acute rejection. Therefore, it is critical to reach target blood concentrations of tacrolimus as soon as possible to improve allograft survival.