Wlodarczyk Z.,Collegium Medicum |
Ostrowski M.,General and Transplantology Surgery |
Mourad M.,Cliniques universitaires Saint Luc |
Kramer B.K.,University of Mannheim |
And 6 more authors.
Therapeutic Drug Monitoring | Year: 2012
Background: Tacrolimus is a well-established immunosuppressive agent for the treatment and prevention of solid organ graft rejection. It is available as an immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged-release, once-daily formulation (Tacrolimus QD). In a previous study of the pharmacokinetics (PK) of these formulations, mean systemic exposure [area under the curve from 0 to 24 hours (AUC0-24)] of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure was similar; however, the mean dose of Tacrolimus QD was higher to achieve similar systemic exposure as Tacrolimus BID. Methods: To further compare the PK of the tacrolimus formulations during the first 2 weeks posttransplant, a substudy was performed in a subset of patients enrolled into a phase III trial in de novo kidney transplant recipients comparing Tacrolimus QD and Tacrolimus BID. To minimize the difference in exposure observed in the earlier study, tacrolimus therapy was initiated before transplant. The PK analysis set comprised 34 patients (17 patients per treatment group) who had 4 complete PK profiles and no major PK-related protocol violations. Results: Mean AUC 0-24 of tacrolimus on day 1 was approximately 16% lower for Tacrolimus QD than for Tacrolimus BID, although by day 3 onward, the exposure was similar between treatment groups. Analysis of dose-normalized AUC0-24 (dose normalized to 0.1 mg/kg) showed a similar pattern. There was a good correlation between AUC0-24 and concentration of tacrolimus at 24 hours postdose for both formulations (Tacrolimus QD, r = 0.87; Tacrolimus BID, r = 0.92), and the slope of the line of best fit was similar. Conclusions: These results suggest that initiating tacrolimus therapy before transplant reduces the difference in exposure between Tacrolimus QD and Tacrolimus BID. © 2012 Lippincott Williams & Wilkins.
Van Hooff J.,Maastricht University |
Van Der Walt I.,Jacaranda Hospital |
Kallmeyer J.,Chelmsford Medical Center |
Miller D.,Christiaan Barnard Memorial Hospital |
And 5 more authors.
Therapeutic Drug Monitoring | Year: 2012
Background: A prolonged-release formulation of tacrolimus for once-daily administration (Tacrolimus QD) has been developed to offer potential improvements in patient adherence. This study compared the pharmacokinetics (PK) of tacrolimus in stable kidney transplant recipients before and after conversion from twice-daily tacrolimus (Tacrolimus BID) to Tacrolimus QD. Methods: This was an open-label, multicenter replicate design study in stable adult kidney transplant recipients (≥6 months posttransplantation) maintained on Tacrolimus BID. Patients underwent four sequential 14-day treatment periods of alternating Tacrolimus BID and QD (mg:mg conversion). Four 24-hour PK profiles were collected, one on the last day of each treatment period. Adverse events were also reported. Results: A total of 60 of 69 patients completed all 4 PK profiles. Steady-state tacrolimus area under the curve from 0 to 24 hours and Cmin were comparable for both formulations, with treatment ratio means (90% confidence intervals) of 92.9% (89.8%-96.0%) and 90.9% (87.3%-94.6%), respectively (acceptance interval: 80%-125%). Both formulations were well tolerated, with renal function remaining stable over the 8-week period. There was a good correlation between area under the curve from 0 to 24 hours and Cmin for Tacrolimus QD and BID (r = 0.88 and 0.82, respectively). The relationship between these two parameters was also similar. Conclusions: The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring. Copyright © 2012 by LippincottWilliams & Wilkins.
Ullah W.,St. Bartholomews Hospital |
Hunter R.J.,St. Bartholomews Hospital |
Haldar S.,Imperial College London |
McLean A.,St. Bartholomews Hospital |
And 6 more authors.
PACE - Pacing and Clinical Electrophysiology | Year: 2014
Background Catheter-based contact force sensing (CFS) technology gives detailed information regarding contact between the catheter tip and myocardium. This may result in more effective ablation procedures. The primary objective of this study was comparison of remote robotic navigation (RRN) and Manual CFS ablation. The secondary objective was to compare CFS with non-CFS ablation for both navigation modes. Methods Prospective registries of consecutive cases undergoing their first ablation for persistent atrial fibrillation (AF) from six hospitals in the United Kingdom and South Africa were analyzed: 50 Manual/CFS and 50 RRN/CFS cases were included. Historical control non-CFS ablation patients were matched by propensity score, giving a total 200 patient cohort. Results RRN/CFS was associated with improved single procedure 1-year success rates (64% vs 36%, P = 0.01) and shorter fluoroscopy times (41% reduction, P < 0.0005) than Manual/CFS ablation, without any difference in procedure times (P = 0.8). The mean contact force was higher in RRN/CFS than Manual/CFS cases (16 [15-18 g] vs 13 [12-15 g], respectively, P = 0.003). Compared with non-CFS historical controls, CFS cases had higher 1-year success rates for RRN (64% vs 36%, P = 0.01), but not Manual ablation (36% vs 38%, P = 1). Procedure times were reduced for CFS cases (20%, P < 0.005 both navigation modes), as were fluoroscopy times (Manual: 43%, RRN 83%, P < 0.005 for both). There were no differences in rates of major or minor complications for either comparison (P > 0.5). Conclusions A combination of RRN and CFS is associated with improved success rates at 1 year and fluoroscopy times for persistent AF ablation, compared with Manual ablation and non-CFS RRN ablation. ©2014 Wiley Periodicals, Inc.
Karabus S.,Christiaan Barnard Memorial Hospital |
Karabus S.,University of Cape Town
Current Allergy and Clinical Immunology | Year: 2012
Stings from bees, bumblebees, wasps and ants usually cause a transient local reaction which may last for several days and which generally resolves without treatment. Occasionally, life-threatening anaphylaxis may occur. Such severe reactions may be refractory to single doses of adrenaline. Each year in the USA about 40 individuals die from anaphylaxis caused by stinging insects. In South Africa, bee-sting hypersensitivity is the most common form of stinging insect allergy. Venom immunotherapy is available and effective for bee venom hypersensitivity but many individuals with stinging-insect allergy are not referred to an allergist for evaluation and are thus never offered this potentially life-saving therapy.
Bai R.,The Texas Institute |
Di Biase L.,The Texas Institute |
Valderrabano M.,Methodist key Heart and Vascular Center |
Lorgat F.,Christiaan Barnard Memorial Hospital |
And 15 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2012
Worldwide Survey on Robotic AF Ablation. Introduction: The Hansen Robotic system has been utilized in ablation procedures for atrial fibrillation (AF). However, because of the lack of tactile feedback and the rigidity of the robotic sheath, this approach could result in higher risk of complications. This worldwide survey reports a multicenter experience on the methodology, efficacy, and safety of the Hansen system in AF ablations. Methods and Results: A questionnaire addressing questions on patient's demographics, procedural parameters, ablation success rate and safety information was sent to all centers where more than 50 robotic AF ablation cases have been performed. From June 2007 to December 2009, 1,728 procedures were performed at 12 centers utilizing the Hansen robotic navigation technology. The overall complication rate was 4.7% and the success rate was 67.1% after 18 ± 4 months of follow-up. In 5 low volume centers there appeared to be a learning curve of about 50 cases (complication rate 11.2% for the first 50 cases vs 3.7% for the 51-100 cases; P = 0.044) and a trend showing a decrease of complication rate with increasing case volume. However, in the remaining 7 centers no learning curve was present and the complication rate was stable over time (3.7% for the first 50 cases vs 3.6% for the 51st case thereafter; P = 0.942). Conclusion: The Hansen robotic system can be used for AF ablation safely. In low volume centers, there appeared to be a learning curve of the first 50 cases after which the complication rate decreased. With a higher case volume, the success rate increased. © 2012 Wiley Periodicals, Inc.