Pneumococcal meningitis before the introduction of 10-valent pneumococcal conjugate vaccine into the National Childhood Immunization Program in Poland

Background

Poland introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into the childhood immunization program in January 2017. During previous decades, considerable changes had occurred in the surveillance system for invasive pneumococcal disease. Therefore, to provide baseline data on pneumococcal diseases before PCV10 introduction, we evaluated the epidemiology of pneumococcal meningitis (PM), the only syndrome monitored consistently since 1970.

Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy

Purpose

A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).

A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54$\mu g/kg\_bw/day$) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) $\mu g/kg\_bw/day$for an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) $\mu g/kg\_bw/day$ for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.     

Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB)

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20–29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999–2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017.After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 μg/L in 2010 to twice the concentration in 2011 (0.31 μg/L) with further increases in 2013 (0.37 μg/L), 2015 (0.59 μg/L) and 2017 (0.70 μg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other.For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 μg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 μg/kg bw/d) was a factor of more than 20 below the TDI.The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.