Clinical practice, resource utilization, and outcomes of device closure of patent foramen ovale in pediatrics.

BACKGROUND: There are few data on patent foramen ovale closure and its outcome in children. In this study, we evaluated the current clinical practice, resource utilization, and outcome of device closure of patent foramen ovale in children. We hypothesized that patent foramen ovale closure would not result in a demonstrated benefit in children. METHODS: We undertook a prospective survey of all consecutive patients (<20 years) who underwent patent foramen ovale closure in our metropolitan area between 1995 and 2010. Differences in proportions were tested using the chi-square test or Fisher's exact test where appropriate. Differences in group medians were tested using Wilcoxon signed-rank test. RESULTS: A total of 153 patients (104 girls), median age 16 years (range 7-19) were studied. Indications for patent foramen ovale closure included: (1) migraine headache (104; 68%), (2) nonmigraine headache (24; 16%), (3) visual symptoms (110; 72%), (4) transient ischemic attack symptoms (42; 28%), and (5) stroke-like symptom (24; 16%). Patent foramen ovale was closed with an Amplatzer septal occluder in 115 (75%) and a Helex septal occluder in 47 (30%). The mean length of hospital stay was 18 ± 11 hours; the mean hospital charge was $24,126 ± $5808. The median duration of follow-up was 12 months, and 80 patients responded to the study survey. On follow-up, symptoms improved in 143 (93%), of which 29 (19%) had a residual shunt. None of the patient or treatment parameters predicted lack of improvement on follow-up. CONCLUSIONS: Despite the lack of proven benefit, children undergo closure of the patent foramen ovale for a variety of reasons, with the vast majority (92%) of patients reporting significant improvement in their symptoms. However, patent foramen ovale closure is an expensive procedure with serious potential complications. Symptomatic improvement even in the presence of a residual shunt suggests a strong placebo effect.

Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation.

BACKGROUND: Pharmacogenetic-guided dosing of warfarin is a promising application of "personalized medicine" but has not been adequately tested in randomized trials. METHODS AND RESULTS: Consenting patients (n=206) being initiated on warfarin were randomized to pharmacogenetic-guided or standard dosing. Buccal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 *3 and VKORC1C1173T with a rapid assay. Standard dosing followed an empirical protocol, whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age, sex, and weight. Prothrombin time international normalized ratio (INR) was measured routinely on days 0, 3, 5, 8, 21, 60, and 90. A research pharmacist unblinded to treatment strategy managed dose adjustments. Patients were followed up for up to 3 months. Pharmacogenetic-guided predicted doses more accurately approximated stable doses (P<0.001), resulting in smaller (P=0.002) and fewer (P=0.03) dosing changes and INRs (P=0.06). However, percent out-of-range INRs (pharmacogenetic = 30.7%, standard = 33.1%), the primary end point, did not differ significantly between arms. Despite this, when restricted to wild-type patients (who required larger doses; P=0.001) and multiple variant carriers (who required smaller doses; P<0.001) in exploratory analyses, results (pharmacogenetic = 29%, standard = 39%) achieved nominal significance (P=0.03). Multiple variant allele carriers were at increased risk of an INR of > or = 4 (P=0.03). CONCLUSIONS: An algorithm guided by pharmacogenetic and clinical factors improved the accuracy and efficiency of warfarin dose initiation. Despite this, the primary end point of a reduction in out-of-range INRs was not achieved. In subset analyses, pharmacogenetic guidance showed promise for wild-type and multiple variant genotypes.