A fresh look at the role of spiramycin in preventing a neglected disease: meta-analyses of observational studies.

PURPOSE: We aimed to investigate the effect of antepartum treatment with spiramycin with or without subsequent pyrimethamine-sulfonamide-folinic acid, compared to no treatment, on the rate of mother-to-child transmission (MTCT) of Toxoplasma gondii (T. gondii) and incidence/severity of sequelae in the offspring. METHODS: Embase and PubMed were searched for literature on spiramycin in pregnant women suspected/diagnosed with T. gondii infection. Meta-analyses were performed using random-effects model. RESULTS: Thirty-three studies (32 cohorts and 1 cross-sectional study), with a total of 15,406 mothers and 15,250 offspring, were pooled for analyses. The MTCT rate for all treated patients was significantly lower than the untreated [19.5% (95% CI 14-25.5%) versus 50.7% (95% CI 31.2-70%), p < 0.001]. The transmission rate in patients on spiramycin monotherapy was also significantly lower than untreated [17.6% (95% CI 9.9-26.8%) versus 50.7% (95% CI 31.2-70%), p < 0.001]. CONCLUSION: Results indicate significant reduction in MTCT rates following spiramycin treatment of suspected/diagnosed maternal T. gondii infection.

Intranasal triamcinolone and growth velocity.

BACKGROUND: Inadequate designs and conflicting results from previous studies prompted the US Food and Drug Administration to publish guidelines for the design of clinical trials evaluating the effects of orally inhaled and intranasal corticosteroids on the growth of children. This study conformed to these guidelines to evaluate the effect of triamcinolone acetonide aqueous nasal spray (TAA-AQ) on the growth of children with perennial allergic rhinitis (PAR). METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluated the effect of once-daily TAA-AQ (110 µg) on the growth velocity (GV) of children aged 3-9 years with PAR by using stadiometry at baseline (4-6 months), during treatment (12 months), and at follow-up (2 months). Hypothalamus-pituitary-adrenal (HPA) axis function was assessed by measuring urinary cortisol levels. Details of adverse events were recorded. RESULTS: Of 1078 subjects screened, 299 were randomized, and 216 completed the study (placebo, 107; TAA-AQ, 109). In the primary analysis (modified intent-to-treat: placebo, 133; TAA-AQ, 134), least-squares mean GV during treatment was lower in the TAA-AQ group (5.65 cm/year) versus placebo (6.09 cm/year). The difference (-0.45 cm/year; 95% confidence interval: -0.78 to -0.11; P = .01), although clinically nonsignificant, was evident within 2 months of treatment and stabilized thereafter. At follow-up, the GV approached baseline (6.70 cm/year) in the TAA-AQ group (6.59 cm/year) and decreased slightly in the placebo group (5.89 cm/year vs 6.06 cm/year at baseline). No HPA axis suppression was observed. CONCLUSIONS: By using rigorous Food and Drug Administration-recommended design elements, this study detected a small, statistically significant effect of TAA-AQ on the GV of children with PAR.

A population pharmacokinetic analysis of milrinone in pediatric patients after cardiac surgery.

The purpose of this study was to ascertain the optimal pharmacokinetic model for milrinone in pediatric patients after cardiac surgery when milrinone was administered as a slow loading dose followed by a constant-rate infusion. The data used for pharmacokinetic analysis were collected in a prospective, randomized, placebo-controlled multi-center trial of milrinone as prophylaxis for the development of low cardiac output syndrome after surgery for repair of complex congenital cardiac defects. Two blood samples were randomly collected from each patient for determination of plasma milrinone concentrations with subsequent population pharmacokinetic modeling. The pharmacokinetics of milrinone in pediatric patients under 6 year's age were best described by a weight-normalized one compartment model after a slow loading dose followed by a constant-rate infusion. The volume of distribution was 482 ml kg(-1) and was independent of age. Clearance was a linear function of age given by Cl = 2.42 ml kg(-1) min(-1) [1 + 0.396*age].

Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease.

BACKGROUND: Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. METHODS AND RESULTS: The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25- microg/kg bolus over 60 minutes followed by a 0.25- microg/kg per min infusion for 35 hours; high dose, 75- microg/kg bolus followed by a 0.75- microg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P=0.023) in 238 treated patients and 64% (P=0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P=0.049). CONCLUSIONS: The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics.

BACKGROUND: Many pediatric patients undergoing cardiac surgery involving cardiopulmonary bypass have a predictable fall in the cardiac index 6 to 18 hours after surgery, the so-called low cardiac output syndrome (LCOS). Because patients who have LCOS require more monitoring and support and have a prolonged stay in the intensive care unit, the syndrome is associated with a costly morbidity. Milrinone, a phosphodiesterase III inhibitor, improves cardiac muscle contractile force and vascular muscle relaxation through positive inotropic and vasodilatory effects. The purpose of the Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics (PRIMACORP) study is to evaluate the safety and efficacy of the prophylactic use of milrinone in pediatric patients at high risk for development of LCOS after undergoing cardiac surgery. METHODS: Patients in the multicenter, randomized, double-blind, placebo-controlled, parallel treatment study will be randomized to 1 of 3 treatment arms: (1) low-dose milrinone (25 microg/kg intravenous bolus over 60 minutes followed by a 0.25 microg/kg/min infusion for 35 hours), (2) high-dose milrinone (75 microg/kg intravenous bolus over 60 minutes followed by a 0.75 microg/kg/min infusion for 35 hours), or (3) placebo. RESULTS: The primary end point for efficacy evaluation will be based on a composite variable consisting of death or development of LCOS requiring additional mechanical or pharmacologic support, up to 36 hours after randomization. A 2-sided test with a 0.025 type I error will be used for the primary end point analysis. The PRIMACORP study will enroll a total of 240 patients. Six additional secondary end points will be analyzed. CONCLUSIONS: The PRIMACORP study will address several questions regarding the safety and efficacy of prophylactic milrinone use in pediatric patients at high risk for development of LCOS after cardiac surgery.