Evaluation of health related quality of life in children with immune thrombocytopenia with the PedsQL™ 4.0 Generic Core Scales: a study on behalf of the pays de Loire pediatric hematology network.

BACKGROUND: Immune thrombocytopenia (ITP) is a childhood disorder that is often life-altering for children and their parents. Health related quality of life (HRQL) has never been chronologically monitored in children with ITP. We initiated a prospective study to assess HRQL from diagnosis to six months and define factors that influence this outcome in children with ITP. METHODS: 73 children with acute ITP aged from 2 to 18 years were prospectively enrolled in the study. According to the presence of bleeding, they were or were not given a 4-day course of corticosteroid treatment. The PedsQL™ 4.0 Generic Core Scale was completed by children and parents upon their inclusion in the study and 6 months after diagnosis. RESULTS: Over the six month period, quality of life improved in terms of their global, physical and psychosocial well-being for 54.5%, 35.6% and 36.2% of patients respectively. This improvement is clinically relevant compared to scores at diagnosis, corresponding at least to a minimal clinically important difference (MCID). Factors such as sex, age, platelet count, bleeding scores, bone marrow aspiration and persistence of ITP at 6 months were not significantly associated with HRQL scores. However, preceding viral infection was identified to have an impact on HRQL. CONCLUSIONS: This first longitudinal study assessing HRQL in children with ITP reveals a global improvement in PedSQL™ 4.0. However, these results should be considered with caution since our data also confirm that self-report HRQL scores are not influenced by any analyzed biologic or clinical parameters. Others tools, such as Kids' ITP Tools, would probably be required to assess the HRQL of this population. TRIAL REGISTRATION: Trial registration clinical trials.gov Identifier: NCT00331357.

Pharmacodynamic equivalence of two flecainide acetate formulations in patients with paroxysmal atrial fibrillation by QRS analysis of ambulatory electrocardiogram.

The pharmacodynamic equivalence of flecainide acetate immediate-release (IR) and controlled-release (CR) formulations was assessed from QRS duration in patients currently treated with the IR formulation. Patients were blindly assigned randomly to the IR (100 mg BID, n = 25) or to the CR group (200 mg OD, n = 23). Electrocardiographic parameters were measured at baseline and at week 8 from 24-h Holter monitoring. Mean (SD) normalized flecainide trough plasma concentration (measured 12 h after last intake) at week 8 was 381.3 ng/ml (104.8) with the IR and 381.4 ng/ml (123.8) with the CR formulation. Hodges-Lehmann estimate (95% CI) of the difference between IR and CR for change in QRS duration between baseline and week 8 was 1.6% (-0.1; 3.7), indicating that the formulations were pharmacodynamically equivalent. Median QRS values (102 vs 100.1 ms at baseline; 103.15 vs 99 ms at week 8) as well as first and third quartiles were very similar in both groups. The correlation between QRS duration and RR classes at baseline was highly significant (P < 0.0001). Correlation coefficient at week 8 was statistically significant for > 50% of the patients and was significant in a greater proportion of patients under the IR compared with the CR formulation. Circadian hourly variations of QRS duration as determined by harmonic analysis showed the occurrence of a peak of QRS widening following each intake of the IR, whereas this pattern was not observed with the CR formulation. The latter results are consistent with a greater occurrence of frequency-dependent QRS variations over the 24-h period with the IR compared with the CR formulation.

Pharmacokinetics and electrocardiographic effects of a new controlled-release form of flecainide acetate: comparison with the standard form and influence of the CYP2D6 polymorphism.

OBJECTIVES: Our objectives were study the single- and repeated-dose pharmacokinetics and electrocardiographic effects (QRS duration) of a new controlled-release form of flecainide acetate compared with the immediate-release form and to examine the influence of CYP2D6 activity. METHODS: Twenty-four healthy subjects (6 men and 6 women at both dosages) received single and repeated doses of 100 or 200 mg immediate-release and controlled-release flecainide in a randomized crossover design. Electrocardiograms were recorded and flecainide plasma concentrations were measured before administration and up to 96 hours after administration. RESULTS: The controlled-release formulation had sustained-release properties, with a significantly lower maximum concentration (C(max)) and delayed time to reach C(max). Compared with the immediate-release formulation, the relative bioavailability of the controlled-release formulation at steady state was 0.85 +/- 0.17 and 0.89 +/- 0.17 for the 100-mg/day and 200-mg/day doses, respectively. Trough flecainide plasma concentration at steady state was bioequivalent for both formulations. Maximum and minimum QRS increases were not significantly different for either the immediate-release or the controlled-release form of flecainide after administration of both single and repeated doses. Mean QRS duration during a dosing interval at steady state correlated with mean plasma concentration for both forms (pooled data; P <.001). The 95% confidence interval for this regression was 26% narrower for the controlled-release form than for the immediate-release form. Flecainide-induced QRS prolongation and pharmacokinetics were not significantly influenced by CYP2D6 activity. CONCLUSIONS: Flecainide-induced QRS prolongation did not differ between the new controlled-release form and the immediate-release form. Flecainide plasma concentrations associated with the new controlled-release form predicted QRS prolongation with less variability compared with the immediate-release form. The CYP2D6 polymorphism did not appear to influence flecainide disposition kinetics or electrocardiographic effects at steady state.