[Efficacy and safety of intravenous immunoglobulins in the management of neonatal hyperbilirubinemia due to ABO incompatibility: a meta-analysis]. / Efficacité et tolérance des immunoglobulines polyvalentes dans l'hyperbilirubinémie néonatale par incompatibilité ABO. Méta-analyse.

OBJECTIVES: ABO fetomaternal red blood cell incompatibility (ABO FMI) induces an immune hemolysis after fetal transfer of hemolyzing maternal anti-A or anti-B. ABO hemolytic disease (ABO HD) remains the most frequent cause of severe and early jaundice in newborns. High levels of unconjugated hyperbilirubinemia may induce acute and chronic neurological complications. Severe hyperbilirubinemia can be prevented by first-line phototherapy (PT) treatment, but exchange transfusion (ET) is required if treatment is not effective, even if ET is linked with high hemodynamic, infectious, gastrointestinal, and/or biological morbidity. Intravenous human polyclonal immunoglobulins (IVIg) have been proposed in concomitant use with PT in order to avoid the requirement for ET in ABO FMI. METHODS: Electronic databases of all published clinical trials in neonatal hyperbilirubinemia due to ABO incompatibility were systematically queried for randomized controlled clinical trials comparing PT alone to PT associated with IVIg based on the requirement for ET. Duration of PT and adverse events were optional criteria. A meta-analysis of the selected data was performed on six selected trials out of 28 found. RESULTS: IVIg doses ranged from 0.5 to 1.5 g/Kg in one to three administrations. Requirement for ET was lower in the IgIV+PT group, with a relative risk of 0.27 [CI 95% 0.17-0.42; P<0.00001], expressed as a number needed to treat of five neonates to avoid one ET. The mean duration of PT was 4 days in the PT group and association of PT with IVIg significantly reduced the duration of PT treatment by 0.84 days. The tolerance of the IVIg and PT association was good with no reported cases of ulcerative enterocolitis in 265 treated newborns. CONCLUSION: IVIG associated with PT reduces the need for ET and the duration of PT in newborns with hyperbilirubinemia due to ABO hemolytic disease. Their efficacy and good tolerance prompt consideration of IVIg as a therapeutic adjuvant to PT in severe hemolytic hyperbilirubinemia due to ABO incompatibility.

Pharmacokinetics and pharmacodynamics of a new highly secured fibrinogen concentrate.

BACKGROUND: Inherited afibrinogenemia is a rare autosomal recessive disorder characterized by the absence or trace amounts of plasma fibrinogen inducing varying bleeding tendencies. Little is known about the pharmacokinetics of plasma-derived fibrinogen concentrates used in the treatment of afibrinogenemic patients. OBJECTIVE: This open, prospective, multicenter study assessed the pharmacokinetic and pharmacodynamic profiles of FIBRINOGENE T1 (FGT1; LFB, Les Ulis, France), a human fibrinogen concentrate treated with three specific biological safety steps. PATIENTS/METHODS: Five adult patients with congenital afibrinogenemia received a single infusion of 0.06 g kg(-1) of FGT1. Plasma samples drawn up to day 14 were assayed for fibrinogen antigen and activity and for coagulation parameters in a central laboratory. RESULTS: Fibrinogen antigen and activity were similar and highly correlated, with very low between-patient variability for pharmacokinetic parameters. Fibrinogen levels increased rapidly and significantly, with a mean plasma concentration of 1.39 g L(-1) being achieved 1 h after the end of the infusion, leading to almost complete in vivo recovery (94%). The mean half-life was 3.4 days, with slow linear elimination, and the distribution was mainly restricted to the vascular compartment. Coagulation parameters were normalized after the infusion and during the following 6-10 days. FGT1 was well tolerated overall. CONCLUSIONS: FGT1 behaves like natural functional fibrinogen, and its pharmacokinetic properties are in line with those expected from a fibrinogen concentrate. Our findings suggest that FGT1 can restore efficient hemostasis in afibrinogenemic patients, and predict good clinical efficacy.

Intravenous immunoglobulin as short- and long-term therapy of multifocal motor neuropathy: a retrospective study of response to IVIg and of its predictive criteria in 40 patients.

OBJECTIVE: To document short-term and long-term responses to a single type of intravenous immunoglobulin (IVIg) in a large cohort of patients with multifocal motor neuropathy (MMN). METHODS: A retrospective study was conducted in 40 patients with MMN included on ENMC Workshop criteria, and treated with periodic IVIg infusions between 1995 and 2003. The short-term response was defined as improvement of at least 1 point on the MRC score in at least two affected muscles at 6 months. The population comprised 22 treatment-naïve patients (who had never received IVIg before inclusion), and 18 previously treated patients. For the long-term evaluation (>6 months), the patients were classified into three groups according to the dependency or not on periodic IVIg. In addition, changes in conduction block (CB) and predictive criteria for response to IVIg were explored. RESULTS: The MRC score significantly improved (p<0.0001) in 14 (70%; 95% CI 0.46 to 0.88) of the 20 treatment-naïve patients (missing data for 2 patients). None of the predictive criteria studied were found to be significant. At the end of follow-up (mean of 2.2+/-2.0 years), only 8 of the 40 patients (22%) had significant remission, whereas 25 patients (68%) were dependent on periodic IVIg infusions. The number of CBs decreased or remained unchanged in 12 treatment-naïve patients and increased in 2 such patients. CONCLUSIONS: This study confirmed a significantly high short-term response to IVIg of patients with MMN, but showed contrasted results in long-term follow-up. No predictive factors for response to IVIg were found.

A multicentre, double-blind, randomized, parallel group study to evaluate the tolerability and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy.

The aim of this study was to determine the tolerability and efficacy of two oral regimens of levetiracetam, 1000 mg and 2000 mg twice daily, as add-on treatment without titration in patients with refractory epilepsy. After a 1- to 4-week baseline, 119 patients were randomized to receive levetiracetam 2000 mg daily, 4000 mg daily, or placebo for a 24-week double-blind period, then levetiracetam 4000 mg daily in a 24-week open-label phase. Somnolence was the most common reason for discontinuation, and along with asthenia, occurred more frequently with levetiracetam than placebo. Responder rates were higher with levetiracetam 2000 mg and 4000 mg daily (48.1% [P < 0.05] and 28.6% [NS], respectively) than placebo (16.1%). In the open-label phase, the overall responder rate was 43.0%. Switching from placebo to levetiracetam increased the overall responder rate from 16.7% to 44.0%. No such increase was observed with patients initiated on levetiracetam 2000 mg daily. Levetiracetam initiated at doses of 2000 mg or 4000 mg daily without titration is well-tolerated and effective as add-on therapy in patients with partial and/or generalized seizures. The higher dose may be related to an increased incidence of somnolence and is not necessarily more effective than the lower dose.

Effectiveness of piracetam in cortical myoclonus.

Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.

Measurement of reaction times in tasks of varying complexity: an indication of the degree and evolution of mental deterioration in the elderly.

In a group of 40 elderly patients with intellectual deterioration, slowing of behaviour was measured with an original reaction time apparatus. Three types of measurements in ascending degree of complexity were evaluated against each other. Intercorrelations, made with indicators of physical, mental and behavioural functioning, demonstrated that ascending complexity in reaction time measurements can be used as an evaluation of the degree of mental deterioration. An example of the use of the apparatus in the evaluation of the improvement after treatment with suloctidil is given.

Double-blind trial of suloctidil versus placebo in moderate to severe mental deterioration.

A double-blind, parallel group, placebo-controlled study was carried out in 30 elderly patients with moderate to severe mental deterioration to assess the effect of suloctidil on their mental condition. A battery of clinical and psychometric evaluations failed to demonstrate any significant differences between the two groups at the end of a 6-month treatment period during which patients received either 200 mg suloctidil or placebo 3-times daily. However, further analysis of the results showed that in the sub-group of patients with moderate mental deterioration on entry, suloctidil treatment produced significant improvement from baseline in the Rey 15 words test and the results were significantly different from those in patients with severe mental deterioration. No consistent changes were observed in the placebo group.