Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children

Background

There were increased reports of fevers and febrile reactions in young children (particularly children aged <5?years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.

Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti‐n‐methyl‐d‐aspartate receptor antibody encephalitis: A retrospective review

Introduction : Anti‐N‐methyl‐d ‐aspartate (NMDA) receptor antibody encephalitis is an increasingly recognized form of autoimmune encephalitis. Conventional treatments include therapies such as corticosteroids, intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE). Although TPE is regularly used for treatment of anti‐NMDA receptor antibody encephalitis, the American Society for Apheresis has given it a category III recommendation only. Earlier administered immunotherapies in tumor‐negative patients may facilitate faster recoveries, but it remains unclear whether or not TPE is superior to steroids and/or IVIG. Methods : We retrospectively evaluated 10 of 14 patients that received steroids and TPE with modified Rankin scores and subjectively assessed the point of largest sustained improvement in all 14 patients. Results : In the patients that received both steroids and TPE at our institution during the same hospitalization (only 10 of 14 patients), 7/10 patients after TPE had improved with the modified Rankin score versus 3/10 patients after steroids. The average modified Rankin score improvement after steroids in this group was ?0.1 as compared with 0.4 after TPE. Based on subjective chart review analysis during which all 14 patients were assessed, the largest sustained improvement occurred immediately following the third–fifth exchange in 9/14 patients, whereas only 2/14 patients appeared to have had significant benefit immediately following steroids. Conclusions : This is compelling preliminary data that suggests that corticosteroids may not be as effective compared to steroids followed by TPE. Given the importance of time‐sensitive treatment, more formal studies may illuminate the ideal first‐line treatment for anti‐NMDA receptor antibody encephalitis. J. Clin. Apheresis 30:212–216, 2015. © 2015 Wiley Periodicals, Inc.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6–59 months of age: A phase 3, randomized,noninferiority study

Background

In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad?/Afluria Tetra?), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete.

Optimization of infusional calcium gluconate for prevention of hypocalcemic reactions during therapeutic plasma exchange

We sought to optimize direct intravenous infusion of calcium gluconate (CaGlu) for maintaining plasma ionized calcium concentration ([Ca²⁺]) and preventing hypocalcemic reactions during 34 consecutive 1-volume therapeutic plasma exchanges (TPEs) in eight patients. CaGlu, 2 g in 50 mL of 0.9% NaCl, was prepared by our hospital pharmacy and infused at either 1.0 or 1.6 g/h during alternate TPE. Plasma [Ca²⁺] was monitored at intervals of 20 to 30 minutes. At 1 g/h of CaGlu, plasma [Ca²⁺] fell by 8.35% after 40 to 50 minutes and then plateaued. At 1.6 g/h of CaGlu, plasma [Ca²⁺] fell by 6% after 20 to 30 minutes and then plateaued. The difference at 40 to 50 minutes was significant (P = .015). Hypocalcemic reactions were noted in three patients during 5 of 17 TPE at 1.0 g/h (all after 40 to 60 minutes) but 0 of 17 TPE at 1.6 g/h (P = .044). CaGlu at 1.6 g/h stabilized plasma [Ca²⁺] and appears to prevent hypocalcemic reactions during TPE.     

Clinical outcomes for early childhood caries: influence of aggressive dental surgery

PURPOSE: The objective of this study was to assess the relationship between the number of stainless steel crowns (SSCs) placed, number of surfaces at risk (SAR) post dental surgery, and the risk for relapse in patients treated for Early Childhood Caries (ECC). METHODS: The study population consisted of 57 children treated for ECC under general anesthesia, ranging in age from 2.3 to 7.3 years old at the time of entry. Dental surgery utilized an aggressive approach: teeth that had necrotic pulps or were nonrestorable were extracted; decayed primary mandibular incisors that could not be treated by stripping were extracted; primary maxillary incisors with 3 or more carious surfaces were extracted; single-surface lesions of primary molars that did not compromise cusp integrity were restored with intracoronal amalgam restorations; primary maxillary, incisors and canines with smooth-surface lesions affecting 2 or less surfaces were treated with intracoronal composites; primary molars and canines requiring vital pulp therapy were restored with SSCs; primary molars with caries lesions affecting 2 or more surfaces (including smooth-surface, white-spot lesions) were restored with SSCs; primary canines with caries affecting 3 or more surfaces were restored with stainless steel crowns; topical fluoride was applied after all restorative therapy was completed. The cohort was examined for new caries lesions 6 months post dental surgery. Relapse was defined as the presence of new smooth-surface caries lesions as defined by Radike. Comparisons between relapse (R) and nonrelapse (NR) groups, with respect to the number of SSCs placed and the number of SAR, were performed using t tests and Wilcoxon tests. A 0.05 level of significance was employed in all statistical tests. RESULTS: Twenty-one of the 57 (37%) patients relapsed. No statistically significant difference for the number of SSCs placed or SAR existed between the R group (SSCs: mean = 4.57, median = 4 +/- 2.18; SAR: mean = 39.76, median = 40 +/- 13.62) and NR group (SSCs: mean=5.44, median = 5.5 +/- 2.62; SAR: mean = 39.98, median = 39.5 +/- 15.19). CONCLUSIONS: The risk for relapse in children treated for ECC is not associated with the number of SSCs placed or SAR; aggressive dental surgery for ECC does not result in acceptable clinical outcomes.     

The effects of different levels of dietary sucrose on root caries subsequent to gingivectomy in conventional rats infected with Actinomyces viscosus M-100

Three groups of weanling, Sprague-Dawley-derived rats were inoculated with Actinomyces viscosus M-100 and fed powdered diet containing either 67%, 5%, or 0% confectioner's sugar. Two further groups were fed diet containing 5% confectioner's sugar and inoculated with Streptococcus sobrinus 6715 or S. sobrinus 6715 plus A. viscosus M-100. The most coronal 1 mm of gingiva was removed from maxillary and mandibular right molar quadrants (gingivectomy), and the animals re-inoculated following gingivectomy. The animals were killed 64 days following gingivectomy, and the lingual surface of mandibular first molar roots was measured for exposed root-surface area and root caries. In the groups of rats infected with A. viscosus M-100, root caries area was significantly greater in the group fed diet containing 67% confectioner's sugar. Sucrose level did not significantly affect the amount of exposed lingual first molar root area regardless of whether the tooth had been subjected to a gingivectomy. In the groups of rats receiving diet containing 5% confectioner's sugar, there were no significant differences in root caries area or exposed root-surface area, regardless of the infection status of the animals. In the rat model presented here, a high level of dietary sucrose was a necessary condition for the initiation of root caries in the absence of other readily fermentable carbohydrates.     

University of North Carolina Caries Risk Assessment Study. III. Multiple Factors in Caries Prevalence

The baseline caries experienced of approximately 5,000 children in South Carolina and Maine was used as the dependent variable in caries risk assessment analyses. Clinical, microbiologic, and demographic factors served as independent variables in a multivariate relationship to caries through regression and discriminant function analyses. Four factors--number of dental visits by the child in the past year, presence of white spot lesions, and both the urgency of need for restorative care and the future caries increment predicted by the examiner--associated significantly and consistently with caries prevalence in primary and permanent teeth of first and fifth graders at both study sites. Several factors associated significantly with caries prevalence at only one site or grade within a site, suggesting that wide applicability of a specific caries risk assessment model may be limited. In these analyses, sensitivity ranged from .60 to .72 and specificity varied from .86 to .91 in the four grade-site groups. The ultimate goal of this longitudinal study is to identify highly caries-prone children in time to prevent the occurrence of a future caries increment. Although the lack of consistent association of many variables, including microbiologic factors, with baseline caries prevalence was unexpected, it is expected that some of these variables will contribute predictive power in the prospective study.