Long-term indoor VOC concentrations assessment a trend analysis of distribution,disposition, and personal exposure in cohort study samples

Inhalation is one of the entry ports for different chemicals into the human body. In order to investigate this application route and its negative health effect to humans, the presence of volatile organic compounds (VOCs) in indoor air is monitored since many years. To assess global trends and changes of the distribution and disposition of VOCs and the corresponding personal exposure, this study analyzed annual indoor air concentrations collected over a period of 9 (2006–2014) years in the context of a birth control cohort study of 72 VOCs. Additionally, Short Time-series Expression Model (STEM) was used to identify certain correlation for VOCs from different compound classes. For ~42 % of the compounds, a tendency to lower annual median indoor air concentrations was found, and for ~10 % of the VOCs, a trend to higher annual median indoor air concentrations. No such tendencies were observed for ~22 % of the investigated compounds. For ~26 % of the VOCs, the applied linear regression model was not suitable to predict global trends as annual median values were not linearly distributed. Mann-Kendall test was used to (i) confirm the results from the linear regression model and to (ii) calculate trends for those compounds, where linear regression was found to be unsuitable. Thus, for only approximately four of the investigated VOCs, no prediction was possible using both statistical approaches. STEM analysis revealed the connection of benzene, ethylbenzene, m+p xylene, α-pinene, 3-carene, pentadecane, and decamethlycyclopentasiloxane, in addition to the correlation of 1-butanol, chlorobenzene, heptanal, and 2-ethyl-1-hexanol concentrations.     

Impfungen bei rheumatischen Erkrankungen des Kindes- und Jugendalters

Vaccinations represent a special problem in children and adolescents with inflammatory rheumatic diseases. There are very limited data on the safety and efficacy of vaccines in these patients, and guidelines for immunization are missing. The immunosuppressive therapy often necessary for these patients gives rise to additional uncertainty. In addition, many colleagues consider vaccination to increase the risk of relapse of the rheumatic illness. As a consequence, there are substantial variations in practicing vaccination in these patients, resulting in insufficient vaccination coverage rates. For example, every third patient with juvenile idiopathic arthritis is incompletely vaccinated; this even includes toxoid vaccines for tetanus and diphtheria. The benefit of vaccinations, which far outweighs their potential risks, is well recognized even in patients with autoimmune diseases. These patients in particular require a special protection from infections due to their immunosuppressive therapies. Therefore, children and adolescents with rheumatic diseases should be immunized according to the Standing Immunization Commission of the Robert Koch Institute recommendations whenever possible. However, the time of vaccination must be carefully selected, taking disease activity and treatment into account.     

The German national registry for primary immunodeficiencies (PID)

In 2009, a federally funded clinical and research consortium (PID–NET, http://www.pid‐net.org ) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID.     

Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 3: Immunoprophylaxis

This paper reviews several specific and nonspecific procedures for immunoprophylaxis to prevent bacteriological infections in preterm and term newborns. An active or passive immunization is limited necessarily by the wide range of organisms causing neonatal infections. There exist first experiences regarding the prophylactic use of intravenous gammaglobulins for high-risk neonates or pregnant women with symptoms of infection and at risk for preterm delivery. Bacterial polysaccharide vaccines are under development, but up to now far off any universal availability.     

Biomonitoring of prenatal analgesic intake and correlation with infantile anti‐aeroallergens IgE

An association between prenatal acetaminophen or ibuprofen intake and an increased risk of asthma and increased IgE level in children is discussed in various epidemiological studies. Although the molecular mechanistic link is still unknown, the question whether or not acetaminophen and/or ibuprofen are safe pain medications during pregnancy arose. In this study, we associate maternal acetaminophen and ibuprofen intake during pregnancy and breastfeeding to infantile asthma phenotypes and elevated IgE level. Therefore, we analysed questionnaires from a local mother–child cohort and monitored drug intake by LC‐MS biomonitoring in urine. No association was found between drug intake and any analysed health outcome using questionnaire data. For the information obtained from biomonitoring, no association was found for ibuprofen and acetaminophen intakes during breastfeeding. However, an association between prenatal acetaminophen intake and increased infantile IgEs related to aeroallergens was statistically detected, but not for asthma phenotypes.     

Establishment of age-dependent reference values for IgA subclasses

BACKGROUND: Recently, subclass-specific antisera have been introduced for application in a nephelometric assay. The aim of this study was to establish age-dependent reference values for serum concentrations of the two IgA subclasses in children and adults. METHODS: Serum levels of IgA1 and IgA2 were measured by automated immunonephelometry in samples from 235 clinically healthy children between 6 months and 18 years of age and 36 healthy adults. RESULTS: Both IgA1 and IgA2 were detectable in all samples, and both IgA1 and IgA2 increased with increasing age. In adults, the mean value for IgA1 is 1.46 g/l for IgA2 0.21 g/l and for total IgA 1.94 g/l. Individual IgA2 values correlate significantly (p < 0.0001) with IgA1 values (r(2) = 0.5433). In addition, there was a highly significant (p < 0.0001) correlation (r(2) = 0.9530) between the measured total IgA and the sum of the two IgA subclasses indicating that immunonephelometry using highly specific polyclonal antisera might be superior to other methods. CONCLUSIONS: These results and the availability of age-dependent reference values make it worthwhile to reassess the role of IgA subclasses in immunodeficiency and autoimmune diseases where conventional methods have led to conflicting results.     

Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan,Europe, and the United States: a Review of 7 Phase 3 Trials

Many patients with primary immunodeficiency (PID) require immunoglobulin G (IgG) replacement therapy, delivered as intravenous IgG (IVIG) or subcutaneous IgG (SCIG). We aim to identify trends in efficacy and safety that would not be evident in individual studies of small patient numbers. Seven open-label, Phase 3, prospective, multicenter studies of the efficacy and safety of Hizentra® (a SCIG), conducted in Japan, Europe, and the US were summarized. Overall, 125 unique patients received 15,013 weekly infusions during a total observation period of 250.9 patient-years. Mean weekly doses of Hizentra® were 83.22–221.3 mg/kg body weight; infusion rates per patient (total body rate) were 25.2–49.3 mL/h across studies. The rates of infections and serious bacterial infections were 3.10 and 0.03 events per patient/year, respectively. Annualized rates of days hospitalized due to infection, out of work/school, and prophylactic antibiotic use were 0.95, 5.14, and 36.78 per patient, respectively. For the equivalent monthly dose, weekly Hizentra® SCIG administration resulted in expectedly-increased serum IgG trough levels in patients switching from IVIG, and maintained levels in patients switching from previous SCIG. Adverse events (AEs) totaled 5039 (events/infusion 0.094–0.773), almost all of which were mild/moderate. Three thousand one hundred ninety-seven were considered treatment-related, the most common of which were injection site reactions (2919 events; 0.001–0.592 AEs per infusion). Systemic AEs were very uncommon. The results from these seven studies indicate that Hizentra® therapy was both efficacious and well tolerated during long-term treatment. This is particularly important in patients with PID, who may require lifelong IgG replacement therapy.