[Hospital readmission induced by adverse drug reaction: a pilot study in a post-emergency unit of a French university hospital]. / Réhospitalisations d'origine médicamenteuse : étude pilote dans un service de post-urgences médicales d'un hôpital universitaire français.

PURPOSE: Adverse Drug Reactions (ADRs) leading to hospital admission was estimated to 3.6 to 21.7%. Despite its importance in terms of patients care, readmission to hospital due to ADRs remains poorly documented. The aim of our study was to investigate the rate and main characteristics of readmission for ADRs. METHODS: We undertook a retrospective study during two years (2011-2012) in the post-emergency unit of Toulouse university hospital (south western, France). We selected all unplanned hospitalization for acute disease and included all cases of patients admitted twice fold or more for ADRs. Characteristics of drug-induced ADRs were assessed according to appropriate use or not. RESULTS: Out of the 197 readmitted patients, 71 was related to ADRs (3.6%) corresponding to 17.8‰ patients-year. Mean age was 82.3 years and 67% were women. The most frequent ADRs found were vascular (n=41, 18.4%), gastro-intestinal (n=28, 12.6%), cardiac (n=28, 12.6%), neurologic (n=26, 11.7%), metabolic (n=26, 10.3%) and psychiatric (n=24, 9.9%). The drugs mainly involved were psychoactive, cardiovascular, digestive or antithrombotic agents. The context of occurrence of ADRs was related to inappropriate drug prescription in 56% of cases. A total of 24 patients were admitted twice for the same ADR and 2 others three times. For 22 patients (30.9%), the same drugs were involved. CONCLUSION: Our data show hospital readmission was due to ADRs in 3.6% of cases. In 1.1% of cases, the same couple "drug-ADR" was involved. Furthermore, in 56% of cases, repeated admissions are related to an inappropriate drug prescription.

Fundoplication and pediatric esophageal manometry: actuarial analysis over 7 years.

Sixty-one children and infants who had significant gastroesophageal reflux and associated complications underwent 73 surgical procedures to control the reflux. In order to evaluate the procedure, several esophageal manograms were obtained from each patient, before, during, and after the operation. Delayed follow-up reports were also obtained from follow-up visits, letter and telephone contact, in order to assess how the patient had progressed. The results were evaluated by actuarial analytic methods. Ninety-four percent of the patients remained alive over the 7-year follow-up period. At the completion of the seventh year, 62% of these patients (actuarially calculated) remained event free. All events occurred within 18 months of surgery. One patient could not be traced at long-term follow-up, which was therefore 92% complete. The 7-year actuarial probability of failure of the fundoplication at this institution is 24% when performed using this technique in these patients. These findings support that manometric calibration of the antireflux procedure tends to give uniform results in pediatric patients, but, compared with other published series has not proved to be superior to procedures that employ only a rubber bougie in the esophagus as an obdurator to prevent a repair that will be too tight.

Human T- and B-cell epitopes of E1 glycoprotein of rubella virus.

The identification of T- and B-cell sites recognized frequently by human populations could provide the basis for selecting the candidate T- and B-cell epitopes for the development of an effective synthetic vaccine against rubella. Rubella virus E1 glycoprotein has been shown to be the predominant antigen to which the majority of human populations develop lymphocyte proliferative and antibody responses. To define the T- and B-cell epitopes of E1 glycoprotein of rubella virus, 23 overlapping synthetic peptides corresponding to more than 90% of the amino acid sequence of E1 were synthesized and tested for their capacities to induce proliferative and antibody responses of 10 seropositive individuals. The most frequently recognized T-cell epitopes were EP19 (residues 324-343), with 7 of 10 responders, and both EP12 (residues 207-226) and EP17 (residues 289-308), with 6 of 10 responders, respectively. Two immunodominant linear B-cell epitopes were mapped to residues 157 to 176 (EP9, 8/10) and 374 to 390 (EP22, 6/10) by using peptide-specific enzyme linked immunosorbent assay.

Localization of the virus neutralizing and hemagglutinin epitopes of E1 glycoprotein of rubella virus.

Current serological assays using whole rubella virus (RV) as a target antigen for detecting RV-specific antibodies fail to define specific RV proteins and antigenic determinants such as hemagglutinin (HA) and virus-neutralizing (VN) epitopes of rubella virus. A panel of E1 deletion mutants and a subset of E1-specific monoclonal antibodies (MAb) were used for the initial analysis of HA and VN epitopes of E1 glycoprotein. A peptide region (E1(193) to E1(269)) was found to contain HA and VN epitopes. Using both overlapping synthetic peptides and truncated fusion proteins within this region, the HA epitope defined by MAb 3D9F mapped to amino acid residues E1(214) to E1(240), while two VN epitopes defined by MAb 21B9H and MAb 16A10E mapped to amino acid residues E1(214) to E1(233) and E1(219) to E1(233), respectively. The epitopes defined in this study are recognized by antibody whether or not the epitopes are glycosylated.

Cellular and humoral immune responses to rubella virus structural proteins E1, E2, and C.

Better understanding of cell-mediated immune responses to rubella virus would provide the basis for the development of safe and effective vaccines against rubella and would aid in analysis of the pathophysiology of congenital rubella syndrome. We have expressed individual rubella virus structural proteins, E1, E2 and C, via vaccinia virus recombinants. Using the expressed recombinant proteins as antigens, we were able to demonstrate antigen-specific lymphocyte proliferative responses in control individuals and individuals with congenital rubella syndrome. Among the two human groups studied, E1 glycoprotein proved to be a better immunogen than E2 or C. For the control individuals, significant differences in proliferative responses to the structural proteins E1, E2, and C were observed. These differences were not significant in individuals with congenital rubella syndrome. In parallel to the lymphoproliferative responses, immunoglobulin G responses were also found directed mainly to the E1 glycoprotein. These results suggest that E1 may be the most important rubella virus antigen to study in determining the domains required for constructing subunit vaccines against rubella.

Analysis of rubella virus E1 glycosylation mutants expressed in COS cells.

cDNA clones encoding the envelope glycoprotein E1 of rubella virus (RV) were altered by site-directed mutagenesis at consensus sites for addition of N-linked glycans. The resulting plasmids were introduced into COS cells and the mutant E1 proteins were analyzed by indirect immunofluorescence, radioimmunoprecipitation, and immunoblotting. We found that RV E1 contains three N-linked oligosaccharides, each approximately 2 kDa in size. Although lack of glycosylation did not appear to affect targeting of E1 to the Golgi region, mutants lacking N-linked glycans at Asn 177 and Asn 209 failed to bind anti-E1 antibodies under nonreducing conditions. Our results suggest that glycosylation may be important for expression of important immunologic epitopes on RV E1.