Alteplase for the Treatment of Catheter Occlusion in Pediatric Patients (March).

Alteplase for the Treatment of Catheter Occlusion in Pediatric Patients (March).

Ann Pharmacother. 2013 Mar 5;
Anderson DM, Pesaturo KA, Casavant J, Ramsey EZ

OBJECTIVE:To review the literature pertaining to the efficacy of alteplase for restoration of patency of occluded venous and dialysis catheters in pediatric patients.DATA SOURCES:A MEDLINE search was conducted and cross-referenced with an EMBASE search through November 2012. Search terms included alteplase, tissue plasminogen activator, and catheter.STUDY SELECTION AND DATA EXTRACTION:Search RESULTS: Fibrinolytics are the drug class of choice for restoration of patency (defined as the ability to withdraw a blood sample) of thrombus-occluded catheters. The trials used to support Food and Drug Administration approval of alteplase for central venous catheter (CVC) occlusions generally had low pediatric enrollment; however, additional small studies are available that support use of alteplase for this indication in children. Alteplase doses of 0.5-2 mg instilled into the lumen of a CVC with dwell times ranging from 30 to more than 240 minutes plus the potential for repeat dosing were reported. Overall efficacy ranged from approximately 50% to 90%, with greater efficacy generally reported with larger doses and longer dwell times. Alteplase doses of 2-2.5 mg with dwell times of 60-120 minutes were observed in 2 studies of occluded peritoneal or hemodialysis catheters, in which efficacy was reported in 57-100% of cases. Limitations of current studies of alteplase for catheter occlusion in children include small study populations and relative lack of pediatric-specific prospective trials.CONCLUSIONS:Alteplase appears to show efficacy for treatment of thrombus-related venous catheter occlusion in pediatric patients; however, data regarding its use in occluded dialysis catheters are limited. HubMed – drug


Pharmacogenetics of Risperidone: A Systematic Review of the Clinical Effects of CYP2D6 Polymorphisms (March).

Ann Pharmacother. 2013 Mar 5;
Cartwright AL, Wilby KJ, Corrigan S, Ensom MH

OBJECTIVE:To summarize and evaluate the pharmacogenetic literature pertaining to the effects of CYP2D6 polymorphism on clinical outcomes of risperidone therapy.DATA SOURCES:A systematic literature search was performed using the search terms risperidone, pharmacogenetics, cytochrome P-450 enzyme system, cytochrome P-450 CYP2D6, and polymorphism (genetic) in MEDLINE (1946-October 2012), EMBASE (1980-October 2012), PubMed (194y-October 2012), International Pharmaceutical Abstracts (1970-October 2012), and Google Scholar.STUDY SELECTION AND DATA EXTRACTION:Identified articles were included if they measured the association between CYP2D6 genetic polymorphisms and clinical outcomes in at least 2 patients taking risperidone. The data elements extracted from these articles consisted of study design, number of subjects, indication for risperidone therapy, CYP2D6 phenotype status, mean daily dose of risperidone, and effects on clinical outcomes.DATA SYNTHESIS:The identified citations consisted of 10 prospective nonrandomized, uncontrolled cohort studies, 1 retrospective cohort study, 1 prospective case-control study, and 1 retrospective case series. Studies were of variable quality and none provided high-quality evidence; they included heterogeneous patient populations with varying clinical diagnoses and drug therapy regimens. Most studies reported nonsignificant trends but were limited by power to detect statistical significance and short trial duration. However, increased risk of adverse effects (including QT interval prolongation) was observed in patients with inactive alleles.CONCLUSIONS:While there were trends toward increased adverse effects in poor metabolizers, most outcomes were not significant. As such, routine genotyping should not be used for screening. Future usefulness cannot be ruled out, as many studies had significant limitations that preclude determination of clinical relevance. Adequately powered clinical and epidemiologic studies are warranted to clarify the role of CYP2D6 genotyping in practice. HubMed – drug


The somatic affairs of BRAF: tailored therapies for advanced malignant melanoma and orphan non-V600E (V600R-M) mutations.

J Clin Pathol. 2013 Mar 5;
Ponti G, Pellacani G, Tomasi A, Gelsomino F, Spallanzani A, Depenni R, Al Jalbout S, Simi L, Garagnani L, Borsari S, Conti A, Ruini C, Fontana A, Luppi G

BRAF V600R-M-D are uncommon mutations, not included in the experimental protocols of BRAF selective inhibitors. We report the evaluation of correlations among different types of BRAF somatic mutations in melanoma and their management with BRAF inhibitors. 21 patients with BRAF mutated metastatic melanoma were enrolled in the protocol with BRAF inhibitors for compassionate use at the University of Modena. Hot spot V600E mutations were found in 19 patients. V600R mutation and double (V600E -V600M) mutation were identified in two melanomas. In one case, V600K mutation was found. Two screening failures were noted. Mean progression free survival at follow-up of to 8 weeks, was 7.6 months. Five patients had a very short follow-up and the experimental protocol is still ongoing, so we cannot provide complete follow-up data. However, all of them are still under treatment and disease progression free. An objective response with few side effects was observed in all patients. in vitro studies with the aim of testing drug sensitivity. HubMed – drug


Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics.

Small. 2013 Mar 6;
Yaehne K, Tekrony A, Clancy A, Gregoriou Y, Walker J, Dean K, Nguyen T, Doiron A, Rinker K, Jiang XY, Childs S, Cramb D

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size. HubMed – drug