A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIII(DTG)), MBNW-derived lung clearance index (LCI), and indices of acinar (S(acin)) and conductive (S(cond)) ventilation inhomogeneity. SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIII(DTG) differed between children with CF and controls, mean±sd was -456.7±492.8 and -88.4±129.1 mg·mol·L(-1), respectively. Abnormal SIII(DTG) was present in 36 (59%) children with CF. SIII(DTG) was associated with LCI (r= -0.58) and S(acin) (r= -0.58), but not with S(cond). In CF, steeply sloping SIII(DTG) potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.

Executive functions in 5- to 8-year olds: Developmental changes and relationship to academic achievement

Pronounced improvements in executive functions (EF) during preschool years have been documented in cross-sectional studies. However, longitudinal evidence on EF development during the transition to school and predictive associations between early EF and later school achievement are still scarce. This study examined developmental changes in EF across three time-points, the predictive value of EF for mathematical, reading and spelling skills and explored children's specific academic attainment as a function of early EF. Participants were 323 children following regular education; 160 children were enrolled in prekindergarten (younger cohort: 69 months) and 163 children in kindergarten (older cohort: 78.4 months) at the first assessment. Various tasks of EF were administered three times with an interval of one year each. Mathematical, reading and spelling skills were measured at the last assessment. Individual background characteristics such as vocabulary, non-verbal intelligence and socioeconomic status were included as control variables. In both cohorts, changes in EF were substantial; improvements in EF, however, were larger in preschoolers than school-aged children. EF assessed in preschool accounted for substantial variability in mathematical, reading and spelling achievement two years later, with low EF being especially associated with significant academic disadvantages in early school years. Given that EF continue to develop from preschool into primary school years and that starting with low EF is associated with lower school achievement, EF may be considered as a marker or risk for academic disabilities.

Mycoplasma-induced minimally conscious state

Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited.

Clinical presentation of celiac disease and the diagnostic accuracy of serologic markers in children

There has been growing recognition of a changing clinical presentation of celiac disease (CD), with the manifestation of milder symptoms. Serologic testing is widely used to screen patients with suspected CD and populations at risk. The aim of this retrospective analysis was to evaluate the clinical presentation of CD in childhood, assess the diagnostic value of serologic tests, and investigate the impact of IgA deficiency on diagnostic accuracy. We evaluated 206 consecutive children with suspected CD on the basis of clinical symptoms and positive serology results. Ninety-four (46%) had biopsy-proven CD. The median age at diagnosis of CD was 6.8 years; 15% of the children were <2 years of age. There was a higher incidence of CD in girls (p = 0.003). Iron deficiency and intestinal complaints were more frequent in children with CD than those without CD (61% vs. 33%, p = 0.0001 and 71% vs. 55%, p = 0.02, respectively), while failure to thrive was less common (35% vs. 53%, p = 0.02). The sensitivity of IgA tissue transglutaminase (IgA-tTG) was 0.98 when including all children and 1.00 after excluding children with selective IgA deficiency. The specificity of IgA-tTG was 0.73 using the recommended cut-off value of 20 IU, and this improved to 0.94 when using a higher cut-off value of 100 IU. All children with CD and relative IgA deficiency (IgA levels that are measurable but below the age reference [n = 8]) had elevated IgA-tTG. In conclusion, CD is frequently diagnosed in school-age children with relatively mild symptoms. The absence of intestinal symptoms does not preclude the diagnosis of CD; many children with CD do not report intestinal symptoms. While the sensitivity of IgA-tTG is excellent, its specificity is insufficient for the diagnostic confirmation of a disease requiring life-long dietary restrictions. Children with negative IgA-tTG and decreased but measurable IgA values are unlikely to have CD.

Visuospatial working memory in very preterm and term born children - Impact of age and performance

Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7–12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.

Delay of cortical thinning in very preterm born children

BACKGROUND: Cortical gray matter thinning occurs during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Preterms show alterations in brain structure, with prolonged maturation of the frontal lobes, smaller cortical volumes and reduced white matter volume. These findings give rise to the question if there is a differential influence of age on cortical thinning in preterms compared to controls. AIMS: To investigate the relationship between age and cortical thinning in school-aged preterms compared to controls. STUDY DESIGN AND OUTCOME MEASURES: The automated surface reconstruction software FreeSurfer was applied to obtain measurements of cortical thickness based on T1-weighted MRI images. SUBJECTS: Forty-one preterms (<32weeks gestational age and/or <1500g birth weight) and 30 controls were included in the study (7-12years). RESULTS: In preterms, age correlated negatively with cortical thickness in right frontal, parietal and inferior temporal regions. Furthermore, young preterms showed a thicker cortex compared to old preterms in bilateral frontal, parietal and temporal regions. In controls, age was not associated with cortical thickness. CONCLUSION: In preterms, cortical thinning still seems to occur between the age of 7 and 12years, mainly in frontal and parietal areas whereas in controls, a substantial part of cortical thinning appears to be completed before they reach the age of 7years. These data indicate slower cortical thinning in preterms than in controls.

Who Is Afraid of School Choice?

This study uses survey data to investigate attitudes among Swiss voters to different models offering more freedom of choice in the educational system. There is a clear opposition to the use of taxpayer money to fund private schools, while free choice between public schools seems to appeal to a majority. The opinions appear to be based on a rational calculation of personal utility. For both types of choice, approval rates are lower for middle to high-income groups and individuals with a teaching qualification. Furthermore, residents of small to medium-sized towns are opposed to more school choice. On the support side, approval rates for private school choice are higher among parents of school-age children and residents in urban areas. The results also indicate differences between the country's language regions, attributable to intercultural differences in what people consider the role of the state.

Implizites Gedächtnis: unwillkürlich, entwicklungsresistent und altersunabhängig

Studied explicit memory and implicit memory performance in children, young adults, and old adults. Human Ss: 21 normal male and female Swiss preschool and school-age children (aged 4 yrs 8 mo to 6 yrs 5 mo) (Exp I). 14 normal male and female Swiss university students (Exp I). 21 normal male and female Swiss preschool and school-age children (aged 5 yrs 3 mo to 6 yrs 10 mo) (Exp II). 21 normal male and female Swiss university students (Exp II). 17 normal male and female Swiss old adults (aged 64–85 yrs) (participants in a course for senior citizens) (Exp III). 14 normal male and female Swiss old adults (aged 73–92 yrs) (nursing home residents) (Exp III). Ss participated in a simple learning task involving visual inspection or naming of pictures. Explicit memory was assessed via free recall and recognition of the stimulus material. Implicit memory was assessed with a perceptual identification task. Age differences in memory performance and in the influence of priming effects on memory performances were analyzed.

Reactivity to Accelerometer Measurement of Children and Adolescents

PURPOSE: Awareness of being monitored can influence participants' habitual physical activity (PA) behavior. This reactivity effect may threaten the validity of PA assessment. Reports on reactivity when measuring the PA of children and adolescents have been inconsistent. The aim of this study was to investigate whether PA outcomes measured by accelerometer devices differ from measurement day to measurement day and whether the day of the week and the day on which measurement started influence these differences. METHODS: Accelerometer data (counts per minute [cpm]) of children and adolescents (n = 2081) pooled from eight studies in Switzerland with at least 10 h of daily valid recording were investigated for effects of measurement day, day of the week, and start day using mixed linear regression. RESULTS: The first measurement day was the most active day. Counts per minute were significantly higher than on the second to the sixth day, but not on the seventh day. Differences in the age-adjusted means between the first and consecutive days ranged from 23 to 45 cpm (3.6%-7.1%). In preschoolchildren, the differences almost reached 10%. The start day significantly influenced PA outcome measures. CONCLUSIONS: Reactivity to accelerometer measurement of PA is likely to be present to an extent of approximately 5% on the first day and may introduce a relevant bias to accelerometer-based studies. In preschoolchildren, the effects are larger than those in elementary and secondary schoolchildren. As the day of the week and the start day significantly influence PA estimates, researchers should plan for at least one familiarization day in school-age children and randomly assign start days.

Development of meta-representations: Procedural metacognition and the relationship to Theory of Mind

In several studies it was shown that metacognitive ability is crucial for children and their success in school. Much less is known about the emergence of that ability and its relationship to other meta-representations like Theory of Mind competencies. In the past years, a growing literature has suggested that metacognition and Theory of Mind could theoretically be assumed to belong to the same developmental concept. Since then only a few studies showed empirically evidence that metacognition and Theory of Mind are related. But these studies focused on declarative metacognitive knowledge rather than on procedural metacognitive monitoring like in the present study: N = 159 children were first tested shortly before making the transition to school (aged between 5 1/2 and 7 1/2 years) and one year later at the end of their first grade. Analyses suggest that there is in fact a significant relation between early metacognitive monitoring skills (procedural metacognition) and later Theory of Mind competencies. Notably, language seems to play a crucial role in this relationship. Thus our results bring new insights in the research field of the development of meta-representation and support the view that metacognition and Theory of Mind are indeed interrelated, but the precise mechanisms yet remain unclear.

Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative

Background:  Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. Objective:  The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. Methods:  We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. Results:  Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0–2 years: adjusted odds ratios (aOR), 1.39 (95%CI, 1.05–1.84)] and with asthma later in childhood in six cohorts [6–8 years: aOR, 1.09(95%CI, 0.90–1.32) and 3–10 years: aOR, 1.10 (95%CI, 0.90–1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6–8 years: aOR, 1.12 (1.02–1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09–1.28)]. Conclusion:  These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.

Isolated extraordinary daytime urinary frequency of childhood: a case series of 26 children in Switzerland

BACKGROUND: The term 'isolated extraordinary daytime urinary frequency' designates an abnormally increased diurnal frequency of painless urination in a completely toilet-trained child with normal urinalysis. METHODS: We report the history of 26 children (16 boys and 10 girls; aged between 4.1 and 10 years) who were referred to us between 2002 and 2006 and subsequently diagnosed with this condition. RESULTS: Possible psychosocial problems, or recent emotional stressors, were disclosed in the majority of the children: recent (36 months or less) asylum seekers (n = 9), school-related problems (n = 4), parental divorce (n = 2) or death of the mother (n = 1). Possible dietary causes were observed in 9 patients: oxalate-rich beverages (n = 5) and liberal ingestion of 'acidic' juices (n = 4). A diet low in oxalates was recommended when children were consuming large quantities of oxalate-rich beverages; and a diet low in acidic juice was recommended in those liberally ingesting acidic juices. Reassurance and observation were the approach in the remaining cases. The median duration of the symptoms was 5 months. A longer (p < 0.05) duration was noted in children of asylum seekers. CONCLUSIONS: This functional condition is easily identifiable, but often under- or misdiagnosed. Confounding the condition might result in redundant investigation.

Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old

BACKGROUND The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ≤ 750 cells/mm(3) or per cent CD4 ≤ 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children. OBJECTIVES To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART. DATA COLLECTION AND ANALYSIS Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity. MAIN RESULTS Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16). AUTHORS' CONCLUSIONS This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations.

When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa

BACKGROUND There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. METHODS AND FINDINGS ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. CONCLUSIONS The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

Impacts of a word-picture training on literacy skills in elementary school children and youths with intellectual disabilities

Objective: There is convincing evidence that phonological, orthographic and semantic processes influence children’s ability to learn to read and spell words. So far only a few studies investigated the influence of implicit learning in literacy skills. Children are sensitive to the statistics of their learning environment. By frequent reading they acquire implicit knowledge about the frequency of letter patterns in written words, and they use this knowledge during reading and spelling. Additionally, semantic connections facilitate to storing of words in memory. Thus, the aim of the intervention study was to implement a word-picture training which is based on statistical and semantic learning. Furthermore, we aimed at examining the training effects in reading and spelling in comparison to an auditory-visual matching training and a working memory training program. Participants and Methods: One hundred and thirty-two children aged between 8 and 11 years participated in training in three weekly session of 12 minutes over 8 weeks, and completed other assessments of reading, spelling, working memory and intelligence before and after training. Results: Results revealed in general that the word-picture training and the auditory-visual matching training led to substantial gains in reading and spelling performance in comparison to the working-memory training. Although both children with and without learning difficulties profited in their reading and spelling after the word-picture training, the training program led to differential effects for the two groups. After the word-picture training on the one hand, children with learning difficulties profited more in spelling as children without learning difficulties, on the other hand, children without learning difficulties benefit more in word comprehension. Conclusions: These findings highlight the need for frequent reading trainings with semantic connections in order to support the acquisition of literacy skills.