Is there an association between socioeconomic status and immune response to infant and childhood vaccination in the Netherlands?

Introduction Socioeconomic status (SES) is a well-known determinant of health, but its relation with vaccine-induced immunity is less documented. We explored the association between SES and immunoglobulin G (IgG) levels against vaccine-preventable diseases in vaccinated children in the Dutch National Immunization Programme. Methods Data from a population-wide cross-sectional serosurvey in the Netherlands (2006–2007) were used. We compared geometric mean IgG concentrations/titers (GMC/T ratios) against measles, mumps, rubella, Haemophilus influenzae type b (Hib), Neisseria meningococcus type C, diphtheria, tetanus, poliovirus types 1,2,3 and pertussis in children of high versus low SES by linear regression analysis. We included 894 children (0–12 years) at one of two timeframes: 1 month to 1 year, or 1–3 years after vaccination. Mother’s educational level and net household income served as binary indicators of SES. Results Of 58 possible associations of vaccine-induced antibody responses with educational level and 58 with income, 10 (9%) were statistically significant: 2 favouring (that is, with higher IgG levels at) high educational level (for Hib 1 m-1y after vaccination (GMC/T ratio: 2.99, 95%CI: 1.42–6.30) and polio 2 1 m-1y after the 9-year booster dose (1.14, 1.01–1.27)) and 8 favouring low income (polio 1, 2 and 3 1 m-1y after the 11-month booster (0.74, 0.58–0.94; 0.79, 0.64–0.97; 0.72, 0.55–0.95), polio 3 and pertussis 1-3y after the 11-month booster (0.70, 0.56–0.88; pertussis-prn: 0.60, 0.37–0.98; pertussis-ptx: 0.66, 0.47–0.95), mumps and rubella 1-3y after first vaccination (0.73, 0.55–0.97; 0.70, 0.55–0.90), and rubella 1 m-1y after second vaccination (0.83, 0.55–0.90)). After adjustment for multiple testing, none of the differences remained significant. There was no association between SES and proportion of children with protective IgG levels

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

Purpose Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. Methods A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. Results A total of 2,852 adult ICU patients were screened of which 1,824 (64 %) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1 %) and sustained coma (4.1 %). CAM-ICU compliance was mean (SD) 82 ± 16 % and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5 % (IQR 12.8–36.6 %). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95 % CI 0.74–0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. Conclusions In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients

The MSX1 allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts

Nonsyndromic orofacial clefts (OFC) are common birth defects caused by certain genes interacting with environmental factors. Mutations and association studies indicate that the homeobox gene MSX1 plays a role in human clefting. In a Dutch case-control triad study (mother, father, and child), we investigated interactions between MSX1 and the parents' periconceptional lifestyle in relation to the risk of OFC in their offspring. We s

Expression of Msx1 and Dlx1 during Dumbo rat head development: Correlation with morphological features

The Dumbo rat possesses some characteristics that evoke several human syndromes, such as Treacher-Collins: shortness of the maxillary, zygomatic and mandibular bones, and low position of the ears. Knowing that many homeobox genes are candidates in craniofacial development, we investigated the involvement of the Msx1 and Dlx1 genes in the Dumbo phenotype with the aim of understanding their possible role in abnormal craniofacial morphogenesis and examining the possibility of using Dumbo rat as an experimental model for understanding abnormal craniofacial development. We studied the expression of these genes during craniofacial morphogenesis by RT-PCR method. We used Dumbo embryos at E12 and E14 and included the Wistar strain as a control. Semi-quantitative PCR analysis demonstrated that Msx1 and Dlx1 are expressed differently between Dumbo and Wistar rats, indicating that their low expression may underly the Dumbo phenotype

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Validation of the Spanish Version of the ICECAP-O for Nursing Home Residents with Dementia

Background Measurement of health-related quality of life (HRQoL) is important for a chronic disease, such as dementia, which impairs the quality of life of affected patients in addition to their length of life. This is important in the context of economic evaluations when interventions do not (only) affect HRQoL and these other factors also affect overall quality of life. Objective To validate the Spanish translation of the ICECAP-O's capability to measure Health-related quality of life in elderly with dementia who live in nursing homes. Method Cross-sectional study. For 217 residents living in 8 Spanish nursing homes, questionnaires were completed by nursing professionals serving as proxy respondents. We analyzed the internal consistency and other psychometric properties. We investigated the convergent validity of the ICECAP-O with other HRQoL instruments, the EQ-5D extended with a cognitive dimension (EQ-5D+C), the Alzheimer's Disease Related Quality of Life (ADRQL) measures, and the Barthel Index measure of activities of daily living (ADL). Results The ICECAP-O presents satisfactory internal consistency (alpha 0.820). The factorial analysis indicated a structure of five principal dimensions that explain 66.57% of the total variance. Convergent validity between the ICECAP-O, EQ-5D+C, ADRQL, and Barthel Index scores was moderate to good (with correlations of 0.62, 0.61, and 0.68, respectively), but differed between dimensions of the instruments. Discriminant validity was confirmed by finding differences in ICECAP-O scores between subgroups based on ADL scores (0.70 low, 0.59 medium, and 0.39 high level care), dementia severity (0.72 mild, 0.63 medium, and 0.50 severe), and ages (0.59 below 75 years and 0.84 above 75 years). Conclusions This study presented the first use of a Spanish version of the ICECAP-O. The results indicate that the ICECAP-O appears to be a reliable Health-related quality of life measurement instrument showing good convergent and discriminant validity for people with dementia

Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans

Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (n = 18) or 0.8 ng/kg of body weight (n = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation

Methods for the guideline-based development of quality indicators--a systematic review

<p>Abstract</p> <p>Background</p> <p>Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.</p> <p>Methods</p> <p>We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.</p> <p>Results</p> <p>From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.</p> <p>Conclusions</p> <p>Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.</p