Geographical differences in first acquisition of Pseudomonas aeruginosa in cystic fibrosis

RATIONALE: Risk of infection with Pseudomonas aeruginosa in cystic fibrosis (CF) may be associated with environmental factors.

OBJECTIVES: To determine whether residential location is associated with risk of first acquisition of P. aeruginosa.

METHODS: We performed bronchoalveolar lavage and upper airway cultures in children newly diagnosed with CF to identify infection with P. aeruginosa during infancy and early childhood. Children were assessed according to their residence in a regional or metropolitan area. Multilocus sequence typing was used to determine P. aeruginosa genotype. An environmental questionnaire was also administered.

MEASUREMENTS AND MAIN RESULTS: A total of 105 of 120 (87.5%) infants diagnosed with CF were included in this study. Diagnosis in 65 infants (61.9%) followed newborn screening at mean age of 4.6 weeks. Sixty subjects (57.1%) were homozygous ΔF508, and 47 (44.8%) were female. Fifty-five (52.3%) infants were regional, of whom 26 (47.3%), compared with 9 of 50 (18.0%) metropolitan children, acquired infection with P. aeruginosa (odds ratio, 4.084; 95% confidence interval, 1.55-11.30). Age at acquisition was similar (regional: median, 2.31 yr; range, 0.27-5.96 yr; metropolitan: median, 3.10 yr, range, 0.89-3.70 yr). Strain typing identified P. aeruginosa genotypes often encountered in different ecological settings and little evidence of cross-infection. Ninety questionnaires (85.7%) were completed. Those who acquired P. aeruginosa were more likely to be living in a household that used water sprinkler systems (P = 0.032), but no differences were identified to explain increased risk of acquisition of P. aeruginosa in regional children.

CONCLUSIONS: Geographical difference in residence of children with CF was associated with increased risk of first acquisition of P. aeruginosa, usually with strains associated with the environment rather than with cross-infection.

Comparison of Microbiomes from Different Niches of Upper and Lower Airways in Children and Adolescents with Cystic Fibrosis

Changes in the airway microbiome may be important in the pathophysiology of chronic lung disease in patients with cystic fibrosis. However, little is known about the microbiome in early cystic fibrosis lung disease and the relationship between the microbiomes from different niches in the upper and lower airways. Therefore, in this cross-sectional study, we examined the relationship between the microbiome in the upper (nose and throat) and lower (sputum) airways from children with cystic fibrosis using next generation sequencing. Our results demonstrate a significant difference in both α and β-diversity between the nose and the two other sampling sites. The nasal microbiome was characterized by a polymicrobial community while the throat and sputum communities were less diverse and dominated by a few operational taxonomic units. Moreover, sputum and throat microbiomes were closely related especially in patients with clinically stable lung disease. There was a high inter-individual variability in sputum samples primarily due to a decrease in evenness linked to increased abundance of potential respiratory pathogens such as Pseudomonas aeruginosa. Patients with chronic Pseudomonas aeruginosa infection exhibited a less diverse sputum microbiome. A high concordance was found between pediatric and adult sputum microbiomes except that Burkholderia was only observed in the adult cohort. These results indicate that an adult-like lower airways microbiome is established early in life and that throat swabs may be a good surrogate in clinically stable children with cystic fibrosis without chronic Pseudomonas aeruginosa infection in whom sputum sampling is often not feasible.

Are the differences in adulthood ill-health across the North-South divide and between Scotland and England also evident in early childhood health indicators?

Regional differences in adult morbidity and mortality within England (i.e., north-south divide or gradient) and between England and Scotland (i.e., Scottish effect) are only partly explained by adult levels of socioeconomic status or risk factors. This suggests variation in early life, and is supported by the fetal origins and life-course literature which posits that birth outcomes and subsequent, cumulative exposures influence adult health. However, no studies have examined the north-south gradient or Scottish effect in health in the earliest years of life. The aims of the study were: i) to examine health indicators in English and Scottish children at birth and age three to establish whether regional differences exist; and ii) to establish whether observed changes in child health at age three were attributable to birth and/or early life environmental exposures. Respondents included 10,639 biological Caucasian mothers of singleton children recruited to the Millennium Cohort Study (MCS) in the year 2000. Outcome variables were: gestational age and birth weight, and height, body mass index (BMI), and externalising behavioural problems at age three. Region/country was categorised as: South (reference), Midlands, North (England), and Scotland. Respondents provided information on child, maternal, household, and socioeconomic characteristics. Results indicated no significant regional variations for gestational age or birth weight. At age three there was a north-south gradient for externalising behaviour and a north-south divide in BMI which attenuated on adjustment. However, a north-south divide in height was not fully explained by adjustment. There was also evidence of a ‘Midlands effect’, with increased likelihood of shorter stature and behaviour problems. Results showed a Scottish effect for height and BMI in the unadjusted models, and height in the adjusted model, but a decreased likelihood of behaviour problems. Findings indicated no regional differences in health at birth, but some regional variation at age three supports the cumulative life-course model.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature

BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation.

OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008.

METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends.

RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ±11 to ±38% (median ±17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours.

CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.

Emotional insecurity in the family and community and youth delinquency in Northern Ireland: A person-oriented analysis across five-waves

Background: Over one billion children are exposed worldwide to political violence and armed conflict. Currently, conclusions about bases for adjustment problems are qualified by limited longitudinal research from a process-oriented, social-ecological perspective. In this study, we examined a theoretically-based model for the impact of multiple levels of the social ecology (family, community) on adolescent delinquency. Specifically, this study explored the impact of children’s emotional insecurity about both the family and community on youth delinquency in Northern Ireland. Methods: In the context of a five-wave longitudinal research design, participants included 999 mother-child dyads in Belfast (482 boys, 517 girls), drawn from socially-deprived, ethnically-homogenous areas that had experienced political violence. Youth ranged in age from 10 to 20 and were 12.18 (SD = 1.82) years old on average at Time 1. Findings: The longitudinal analyses were conducted in hierarchical linear modeling (HLM), allowing for the modeling of inter-individual differences in intra-individual change. Intra-individual trajectories of emotional insecurity about the family related to children’s delinquency. Greater insecurity about the community worsened the impact of family conflict on youth’s insecurity about the family, consistent with the notion that youth’s insecurity about the community sensitizes them to exposure to family conflict in the home. Conclusions: The results suggest that ameliorating children’s insecurity about family and community in contexts of political violence is an important goal toward improving adolescents’ well-being, including reduced risk for delinquency.

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies

PURPOSE: The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers.

DESIGN: Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).

RESULTS: The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.

CONCLUSIONS: Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested. 

Primary airway epithelial cell culture and asthma in children-lessons learnt and yet to come

Until recently the airway epithelial cell (AEC) was considered a simple barrier that prevented entry of inhaled matter into the lung parenchyma. The AEC is now recognized as having an important role in the inflammatory response of the respiratory system to inhaled exposures, and abnormalities of these responses are thought to be important to asthma pathogenesis. This review first explores how the challenges of studying nasal and bronchial AECs in children have been addressed and then summarizes the results of studies of primary AEC function in children with and without asthma. There is good evidence that nasal AECs may be a suitable surrogate for the study of certain aspects of bronchial AEC function, although bronchial AECs remain the gold standard for asthma research. There are consistent differences between children with and without asthma for nasal and bronchial AEC mediator release following exposure to a range of pro-inflammatory stimulants including interleukins (IL)-1β, IL-4, and IL-13. However, there are inconsistencies between studies, e.g., release of IL-6, an important pro-inflammatory cytokine, is not increased in children with asthma relative to controls in all studies. Future work should expand current understanding of the "upstream" signalling pathways in AEC, study AEC from children before the onset of asthma symptoms and in vitro models should be developed that replicate the in vivo status more completely, e.g., co-culture with dendritic cells. AECs are difficult to obtain from children and collaboration between centers is expected to yield meaningful advances in asthma understanding and ultimately help deliver novel therapies. 

Seeking the New Normal? Troubled Spaces of Encountering Visible Differences in Warsaw

In times of globalisation and super-mobility, ideas of normality are in turmoil. In different societies in, across and beyond Europe, we face the challenge of undoing specific notions of normality and creating more inclusive societies with an open culture of learning to live with differences. The scope of
the paper is to introduce some findings on encounters with difference and negotiations of social values in relation to a growing visibility of difference after 1989 in Poland, on the background of a critique of normality/normalisation and normalcy.On the basis of interviews conducted inWarsaw, we investigate how normality/normalisation discourses of visible homosexuality and physical disability are incorporated into individual self-reflections and justifications of prejudices (homophobia and disabilism). More specifically we argue that there are moments of ‘cultural transgressions’ present in everyday practices towards ‘visible’sexual and (dis)ability difference.

Technological aids for the rehabilitation of memory and executive functioning in children and adolescents with acquired brain injury (Review).

Background The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision. We have systematically reviewed studies examining the effects of technology-based interventions for the rehabilitation of deficits in memory and executive functioning in children and adolescents with acquired brain injury. Objectives To assess the effects of technology-based interventions compared to placebo intervention, no treatment, or other types of intervention, on the executive functioning and memory of children and adolescents with acquired brain injury. Search methods We ran the search on the 30 September 2015. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic + EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), CINAHL Plus (EBSCO), two other databases, and clinical trials registers. We also searched the internet, screened reference lists, and contacted authors of included studies. Selection criteria Randomised controlled trials comparing the use of a technological aid for the rehabilitation of children and adolescents with memory or executive-functioning deficits with placebo, no treatment, or another intervention. Data collection and analysis Two review authors independently reviewed titles and abstracts identified by the search strategy. Following retrieval of full-text manuscripts, two review authors independently performed data extraction and assessed the risk of bias. Main results Four studies (involving 206 participants) met the inclusion criteria for this review. Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants. Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of bias We assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high. One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placebo Results from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to -0.09; P = 0.62; I2 = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen’s rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant. The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: Memory One small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomes Two studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I2 = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect. A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). Authors' conclusions This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement.

Characteristics of change triggered temper outbursts in children with PWS and ASD and how these may impact on the efficacy of behavioural intervention strategies.

Background
Temper outbursts are prevalent in individuals with PWS and are often triggered by unexpected changes to routines or plans. However, such outbursts are also common in individuals with several other neurodevelopmental disorders, including those with a diagnosis of autism spectrum disorder (ASD). We compared the profile of temper outbursts in children with PWS to that in children with ASD. We examined whether differences in the temper outburst profile predicted differences in the outcomes of two caregiver led intervention strategies aiming to reduce change triggered outbursts.
Methods and results
Thirteen 7-15 year olds with PWS – taking part in a larger study involving 60 children evidencing temper outbursts following changes – were individually matched for age to children with ASD (mean ages: 10.70; 10.76 yrs). Caregivers participated in a structured/semi-structured interview on children's outbursts; completed a web-based outburst diary over a 6 month baseline; and are currently using either a change signalling intervention to reliably warn children of forthcoming changes; or a planning ahead intervention to reduce children's exposure to unexpected changes.
As reported at interview, on average, children with PWS showed more frequent temper outbursts than those with ASD (closer to daily vs. weekly). For seven children with PWS and six with ASD, 60% or more of their temper outbursts were reported to be triggered by changes. Whilst outbursts had similar durations when triggered by changes or by other events in children with PWS; change triggered outbursts in children with ASD were generally shorter. The most commonly reported outburst components in children with PWS included indicators of heightened emotional arousal but this was not the case for children with ASD. Data on behavioural change associated with each of the intervention strategies will be discussed.
Conclusions
Change triggered temper outbursts can be a problem for children PWS and ASD, however subtle differences appear to exist in the profile of these outbursts. Some of these differences may be relevant for the expected efficacy of different behavioural intervention strategies that target outbursts.
Summary
Temper outbursts (tantrums) were compared in children with PWS or autism spectrum disorder before and during use of one of two helping strategies. Helping strategies were led by caregivers and aimed to reduce outbursts that follow changes to routines or plans by making such changes more predictable, or by reducing the quantity of changes. Characteristics of outbursts may be important to help us predict which helping strategies may be most effective.