Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia

There is limited safety information about ferric carboxymaltose (FCM), a new intravenous iron preparation. This randomized, crossover study compared the safety and tolerability of double-blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia. Subjects (559) with iron deficiency anemia received a dose of either FCM (15 mg/kg, maximum 1000 mg) over 15 minutes or placebo on day 0. On day 7, subjects received the other agent. Safety evaluations were performed on days 7 and 14. The primary endpoint was the incidence of treatment-emergent adverse events during each 7-day study period. During the first 24 hours and during the 7-day treatment period, at least one treatment-emergent adverse event was experienced by 15.0% and 29.3% of subjects after FCM and 11.4% and 19.7% after placebo, respectively. Most were classified as Grade 1 or 2. Six subjects had Grade 3 treatment-emergent adverse events after FCM and 9 subjects after placebo. One subject had a Grade 4, and 1 subject had a Grade 5 treatment-emergent adverse event, but neither was considered study drug-related. During the first 24 hours of the treatment period, drug-related adverse events were reported in 9.3% of subjects receiving FCM and 4.8% receiving placebo. Of drug-related Grade 3 events, 4 subjects received FCM and 5 subjects received placebo. Administration of FCM (15 mg/kg, maximum of 1000 mg) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78671/1/j.1542-4758.2009.00409.x.pd

Gentamicin pharmacokinetics during slow daily home hemodialysis

Gentamicin pharmacokinetics during slow daily home hemodialysis.BackgroundGentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmacokinetics for SDH hemodialysis patients.MethodsEight patients (four male and four female) received a single intravenous dose of 0.6 mg/kg gentamicin post-hemodialysis. Blood samples were collected at 5, 10, 15, 30, and 60 minutes after dose. The next day patients underwent a typical SDH hemodialysis (high-flux F50NR dialyzer) session. Blood samples were taken at 0, 5, 15, 60, 120, 240, 360, 480 minutes during and 15, 30 and 60 minutes post-hemodialysis. Baseline and 24-hour urine samples were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model.ResultsPatients were 42.5 ± 13.1 years old (mean ± SD). Inter-, intra-, and post-hemodialysis collection periods were 17.0 ± 2.1 hours, 8.1 ± 0.4 hours, and 1.1 ± 0.1 hours, respectively. Intra-, and interdialytic gentamicin half-lives were different (intradialytic, 3.7 ± 0.8 hours; interdialytic, 20.4 ± 4.7 hours; P < 0.0001). Hemodialysis clearance accounted for 70.5% gentamicin total clearance. Renal clearance correlated with glomerular filtration rate (GFR) (renal clearance = 1.2 GFR; r2 = 0.98; P < 0.001). Mean peak and trough of hemodialysis concentrations were 1.8 ± 0.6 μg/mL and 0.5 ± 0.2 μg/mL, respectively. Post-hemodialysis rebound was 3.1 ± 8.8% at 1 hour.ConclusionPharmacokinetic model predicts 2.0 to 2.5 mg/kg dose gentamicin post-hemodialysis would provide peak (1 hour post-dose) and trough (end of SDH hemodialysis session) concentrations of 6.0 to 7.5 μg/mL and 0.7 to 0.8 μg/mL, respectively. This would provide adequate coverage for most gram-negative organisms in SDH hemodialysis patients

The European Union, borders and conflict transformation: the case of Cyprus

Much of the existing literature on the European Union (EU), conflict transformation and border dynamics has been premised on the assumption that the nature of the border determines EU intervention and the consequences that flow from this in terms of EU impact. The article aims to transcend this literature through assessing how domestic interpretations influence EU border transformation in conflict situations, taking Cyprus as a case study. Moreover, the objective is to fuse the literature on EU bordering impact and perceptions of the EU’s normative projection in conflict resolution. Pursuing this line of inquiry is an attempt to depart from the notion of borders being constructed solely by unidirectional EU logics of engagement or bordering practices to a conceptualization of the border as co-constituted space, where the interpretations of the EU’s normative projections by conflict parties, and the strategies that they pursue, can determine the relative openness of the EU border