A human anti-D monoclonal antibody selected for enhanced FcgammaRIII engagement clears RhD+ autologous red cells in human volunteers as efficiently as polyclonal anti-D antibodies.

A human anti-RhD immunoglobulin G1 monoclonal antibody (mAb), R297, was tested in a phase I study to assess its ability to induce the clearance of antibody-coated autologous RhD+ red blood cells (RBCs) in healthy male volunteers. The clearance potency of R297 was compared with that of a marketed human polyclonal anti-D product (Rhophylac). This mAb has been selected for its ability to strongly engage Fc-gamma receptor IIIA and to mediate a potent antibody-dependent cell cytotoxicity (ADCC) against RhD+ RBCs. Autologous RhD+ RBCs were sensitized with either Rhophylac or R297 at three different coating percentages (25, 12.5 and 6.25%), before re-infusion. This phase I study showed that the human R297 mAb promoted rapid and complete clearance of RBCs, and showed activity that was at least as potent as the human polyclonal anti-D antibody preparation. Clearance of RBCs could still be observed when the percentage of R297 used to coat the RBCs was reduced to 6.25%. Finally, none of the adverse events was severe or considered to be related to R297. Thus, R297 is a promising candidate for the prevention of allo-immunization and represents a new generation of Fc-modified monoclonal antibodies with increased FcgammaRIII binding and increased ADCC.

[Comparative study of hospital costs associated with human albumin 20% (Vialebex 20%) or polygeline as a fluid resuscitation strategy for cirrhotic ascites]. / Etude comparative des coûts hospitaliers liés à une stratégie de remplissage vasculaire par albumine humaine à 20% (Vialebex 20%) ou par polygéline dans le traitement des ascites cirrhotiques.

OBJECTIVES: To compare the hospital costs associated with two fluid resuscitation strategies for cirrhotic ascites: one with human albumin 20% (Vialebex 20%) and one with polygeline. METHODS: Multicenter prospective randomized double-blinded comparative trial (that also compared efficacy and tolerance). The economic evaluation was based on direct medical costs throughout the follow-up period: days of hospitalization, hospital consultations, medical procedures, and fluid resuscitation products. This cost-minimization study had a 6-month follow-up period. Daily costs in euros were adjusted over a 30-day period. The study was interrupted prematurely because of an alert due to the bovine origin of the polygeline, and the inclusion objectives could therefore not be met. RESULTS: The economic analysis included all patients in the efficacy population (group receiving human albumin 20%: n=30, polygeline group: n=38). It found a standardized cost per patient for 30 days of treatment that was significantly lower (p=0.004) for human albumin 20% (median: 1915 euro; range: 1330-4105) than for polygeline (median: 4612 euro; range: 2138-12234). This difference is related mainly to a reduction in the frequency and duration of hospitalization in specialized units, but also to other aspects of management: hospitalization in other departments, specific solutions for the study products, and hospital procedures. CONCLUSION: The economic results of this trial favor a fluid resuscitation strategy that uses human albumin 20% for cirrhotic patients. They are consistent with the clinical results and help assess the cost-benefit ratio of human albumin 20% for this indication.

Clinical efficacy of piracetam in cognitive impairment: a meta-analysis.

A meta-analysis has been performed including nineteen double blind, placebo controlled studies with piracetam in patients suffering from dementia or cognitive impairment in the elderly. These studies had as common outcome measure a clinical global impression of change, a measure of clinically meaningful improvement. The meta-analysis of this global outcome followed the methodology set forward by the Cochrane Collaboration. This article describes the studies, the patient populations and the methods of data extraction. The results of the meta-analysis demonstrate a difference between those individuals treated with piracetam and those given placebo, both as significant odds ratio and as a favourable number needed to treat. While there may be problems in meta-analyses and the interpretation of the statistical results, the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment.