Efficacy, immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known. Objective: A systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics. Methods: The protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics. Results: We retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014). Conclusions: More evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population

Development and Evaluation of the ES-2 Dummy

Over the last year, the European Enhanced Vehicle-safety Committee Working Group 12 has assessed and reviewed the performance of the enhanced anthropomorphic test device for lateral impacts, EUROSID-2 (ES-2). The objectives for this work have been the following: - To verify whether the proposed design is addressing the shortcomings of the regulatory test device EUROSID-1 as identified previously by EEVC and NHTSA- To make sure that the original EUROSID-1 biofidelity and performance in normal test conditions is preserved. - To reach a well-balanced conclusion, the working group has undertaken a test program to assess the most important requirements for the ES-2 dummy, biofidelity, sensitivity, repeatability, handling, durability, certification and full-scale performance in comparison with EUROSID-1.In addition, but no less important, the working group has reviewed and explored the findings of full-scale tests conducted at several member organisations within ACEA. ACEA has reported the most important findings in September 2000. Subsequently, WG 12 has further investigated the issues raised in this report. On the basis of this work, the working group has concluded the following with regards to the ES-2 specifications and performance:The ES-2 prototype as tested is superior to current test device EUROSID-1 and, hence, a more appropriate test device for regulatory testing. The important shortcomings of the EUROSID-1 have been satisfactorily addressed with ES-2, whilst biofidelity is maintained, in some areas even somewhat improved. It should be noted, however, that the assessment of thorax biofidelity was based on deflection and force-time data only, and does not incorporate an assessment of V*C. It is recommended to adopt the hardware design without further modification and to use the new proposed certification procedures, with the exception of the high velocity pelvis test.Overall test results in full-scale tests have shown that some critical dummy measurement values for ES-2 have increased compared to EUROSID-1, in particular rib deflection, 17%, and V*C, 23%1 on average. Other values on the other hand have brought down such as the pubic force (10%) due to improved leg interaction. Contrary to the full-scale results, the ES-2 gave equal or lower values for all critical measurements in the biofidelity tests.For the large majority of vehicles tested, the different results would not affect pass or fail with respect to current regulatory limits. It should be noted, however, that, maintaining the rating levels in consumer testing, ES-2 results would lead motoring consumers to believe the protection offered in side impact has decreased while in fact the safety performance of these vehicles has not changed.A force transducer has been developed to measure the force applied to the back plate. It is recommended to use the force transducer in full vehicle assessment.Finally, the working group believes the ES-2 dummy forms a solid basis for interim harmonisation and will further support activities to help realise this objective

Is retesting in growth hormone deficient children really useful?

Patients with childhood-onset GH deficiency (GHD) are usually retested after achievement of near final height, to verify whether they need to continue GH treatment. We investigated if GH stimulation test is necessary to confirm a persistent status of GHD or if other parameters could be a reliable predictors of GHD persistence. METHODS: 164 children with idiopathic GHD (55 females and 109 males) were retested when they reached near final height using GH releasing hormone (GHRH)+arginine test or arginine alone. RESULTS: At diagnosis, 23.8% of patients showed severe GHD (GH peak at diagnosis <5 ng/ml) and 76.2% showed partial GHD (GH peak <10 ng/ml). At time of retesting, 82.1% of severe GHD and 82.4% of partial GHD patients showed transient GHD. IGF-I levels were not different between persistent (0.18±1.18 SDS) and transient GHD subjects (0.17±0.82 SDS). Furthermore, among persistent severe GHD patients only two showed very reduced levels of IGF-I (<-2.0 SDS). CONCLUSIONS: The majority of patients idiopathic GHD proved to be transient. IGF-I levels alone do not discriminate subjects with persistent from those with transient GHD. Therefore, after the end of GH substitutive treatment, a re-evaluation of GH secretion is mandatory to verify the persistence of GHD in adulthood