Clonidine 1 μg/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA).Invasive aspergillosis (IA) remains an important cause of infectious morbidity and mortality in immunocompromised patients. It is the most common invasive fungal disease (IFD) in patients with hematological malignancies (5). Current first-line therapies with liposomal amphotericin B and voriconazole fail in approximately 50% of patients. With 12-week mortality rates as high as 28%, new approaches are urgently needed (7, 12).High-dose liposomal amphotericin B (i.e., 10 mg/kg per day for the first 2 weeks of treatment) did not yield better outcomes than a standard dose of 3 mg/kg per day but resulted in higher rates of renal adverse events (AEs) (7). Dose escalation of voriconazole is not pursued due to the nonlinear disposition of the compound and a narrow therapeutic window. Antifungal combination therapy is another attractive strategy, but it has yet to be proven superior to monotherapy (22).Caspofungin is generally well tolerated and exhibits favorable pharmacokinetic properties (21). Unlike the triazoles, it is not metabolized through the cytochrome P450 enzyme system (11). The drug had excellent efficacy and safety results in clinical trials of candidiasis (1,17,23,24) and was effective as salvage therapy for IA after amphotericin B or itraconazole proved ineffective or toxic (15), and a large-scale study in neutropenic patients with persistent fever demonstrated an efficacy similar to that of liposomal amphotericin B but improved tolerability (26). Two recently published trials investigated the caspofungin standard maintenance doses of 50 mg once a day (QD) for first-line treatment of IA and yielded response rates of 33 and 42% (13, 25). While these response rates were below the expected outcomes (7, 12), they have been attributed to the severely ill patient groups enrolled in these trials and the rigorous enforcement of the EORTC/MSG

No abstract

The combination of topotecan, cyclophosphamide, and etoposide is tolerable and effective in relapsed and untreated neuroblastoma. Myelotoxicity is the main side effect but seems justified in view of the encouraging response rates. A randomized phase-III trial in primary disease has been commenced.

Background: Short-acting opioids like remifentanil are suspected of an increased risk for tolerance, withdrawal and opioid-induced hyperalgesia (OIH). These potential adverse effects have never been investigated in neonates. Objectives: To compare remifentanil and fentanyl concerning the incidence of tolerance, withdrawal and OIH. Methods: 23 mechanically ventilated infants received up to 96 h either a remifentanil- or fentanyl-based analgesia and sedation regimen with low-dose midazolam. We compared the required opioid doses and the number of opioid dose adjustments. Following extubation, withdrawal symptoms were assessed by a modification of the Finnegan score. OIH was evaluated by the CHIPPS scale and by testing the threshold of the flexion withdrawal reflex with calibrated von Frey filaments. Results: Remifentanil had to be increased by 24% and fentanyl by 47% to keep the infants adequately sedated during mechanical ventilation. Following extubation, infants revealed no pronounced opioid withdrawal and low average Finnegan scores in both groups. Only 1 infant of the fentanyl group and 1 infant of the remifentanil group required methadone for treatment of withdrawal symptoms. Infants also revealed no signs of OIH and low CHIPPS scores in both groups. The median threshold of the flexion withdrawal reflex was 4.5 g (IQR = 2.3) in the fentanyl group and 2.7 g (IQR = 3.3) in the remifentanil group (p = 0.312), which is within the physiologic range of healthy infants. Conclusions: Remifentanil does not seem to be associated with an increased risk for tolerance, withdrawal or OIH.