The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly

In young children, polyvalent pneumococcal polysaccharide conjugate vaccines (PCVs) have been shown to offer advantage over plain polysaccharide vaccines (PPVs) in both immunogenicity and priming for memory responses. In the elderly, the potential benefit of conjugate vaccines is unclear.     

Antibody forming cells and plasmablasts in peripheral blood in CVID patients after vaccination

Common variable immunodeficiency (CVID), the most frequent primary antibody disorder, is characterized by hypogammaglobulinaemia and impaired antibody production. Poor vaccination response is essential for the diagnosis of CVID. Their under laying defects remain to be elucidated. Routine determination of antibody production in serum from CVID patients after vaccination and investigation of B cell function in vivo is complicated due to substitution therapy. Therefore we investigated antibody production on the B-cell level by ELISPOT and characterized changes in B-cell subpopulations in CVID patients, including plasmablasts, in peripheral blood by flow cytometry after vaccination for specification of the diagnosis. Thirty-seven CVID patients and eighty healthy volunteers were immunized with tetanus toxoid and pneumococcal polysaccharide vaccines. Specific antibody levels and B cell subpopulations were measured before vaccination and on day 7 after vaccination by ELISPOT assay and flow cytometry respectively. Of the thirty-seven well defined CVID patients studied, thirty lacked detectable spot forming cells producing specific IgG, IgA or IgM antibodies against employed vaccines and seven had only weak responses compared to controls. In the control group, an increase in circulating plasmablasts on day 7 post immunization corresponded with the appearance of antibody forming cells. In contrast, CVID patients failed to increase plasmablasts significantly in peripheral blood after antigen challenge. Our findings indicate that CVID patients have a block in terminal B-cell differentiation and that flow based assessment of plasmablasts in peripheral blood after vaccination serves as a surrogate diagnostic marker for assessing in vivo antibody responses in patients suspected to have CVID.     

Oligosaccharides as anti-angiogenic agents

Background: Several studies of drugs that inhibit tumour angiogenesis have shown improvements in the survival of cancer patients, thus validating angiogenesis as a clinically relevant target. Both intracellular and extracellular approaches have shown promising results in clinical situations. Objectives: To compare and contrast oligosaccharide therapies and other anti-angiogenic compounds for their benefits and toxicity. Methods: Analysis of the relevant literature including presentations at recent conferences. Results: Receptor tyrosine kinase inhibitors are orally available but have a broad spectrum of activity which is associated with toxicity. Antibodies are associated with different toxicities, however, they are administered parenterally. Oligosaccharides that act as competitive inhibitors of heparan sulfate (HS) are in the early and late phases of clinical development. The advantage of oligosaccharides should be that they can be designed to target several angiogenic molecules, that they are relatively safe and that they can be administered subcutaneously at home. The key questions concerning their development focus on whether compounds with sufficient affinity and relative specificity can be generated, whether they are active at doses that do not perturb the coagulation cascade to a clinically dangerous level, whether the synthetic routes are scalable and, whether the current Phase III trials will yield positive results. Conclusions: Saccharides represent a novel and exciting therapeutic approach that targets a spectrum of angiogenic molecules that cannot be inhibited through established drug development programmes.     

Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine

Background

Data on duration of protection against invasive meningococcal disease post-vaccination with the recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) are limited. We evaluated bactericidal activity persistence in adolescents/young adults up to 7.5?years post-primary vaccination with 4CMenB, and response to a booster dose compared with vaccine-naïve controls.

Has the Medicare Prospective Payment System Led to Increased Nursing Home Efficiency?

RESEARCH OBJECTIVE: To assess the impact of recent Medicare prospective payment system (PPS) changes on efficiency in skilled nursing homes. DATA SOURCE/STUDY SETTING: Medicare Cost Reports (MCR), On-line Survey Certification and Reporting System (OSCAR), Area Resource Files (ARF), a Centers for Medicare and Medicaid Services (CMS) hospital wage index website, a Consumer Price Index (CPI) database, and a survey of state Medicaid reimbursement rates. The sample was 8,361 nursing homes in the Medicare Cost Report databases from the years 1997 to 2003. STUDY DESIGN: Data-envelopment analyses (DEA) calculated efficiency scores for three separate DEA models: unadjusted, acuity-adjusted, and acuity-and-quality-adjusted efficiency. The efficiency scores from these models were regressed on the Medicare PPS changes (the Balanced Budget Act [BBA], the Balanced Budget Refinement Act [BBRA] and the Benefits Improvement and Protection Act) and other organizational and market explanatory variables using a panel-data truncated regression. PRINCIPAL FINDINGS: Mean values for all efficiency measures decreased over time, the acuity-quality-adjusted efficiency measures decreasing the most. All policy variables were significantly negatively related to all efficiency measures. Higher nurse staffing was negatively related to efficiency in all but the acuity-quality-adjusted model. Other explanatory variables varied in their relationships to the efficiency variables. CONCLUSIONS: The results suggest that the reimbursement policy changes had a significantly negative impact on efficiency. Higher nurse staffing contributed to lower efficiency only when efficiency was not adjusted for quality. Various organizational and market factors also played significant roles in all efficiency models.     

Therapeutic effect of bilastine in Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber)

Background

Environmental exposure chambers have been used to expose subjects to aeroallergens to investigate the efficacy of prophylactic treatment with symptomatic agents in Japan. We first examined the therapeutic effect of bilastine (BIL), a novel non-sedative second-generation H₁-antihistamine, in subjects with Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber).