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.

Adherence to treatment in children and adolescents with cystic fibrosis: a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms

BACKGROUND: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence.

METHODS: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale.

RESULTS: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence.

CONCLUSIONS: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children.

Exhaled breath temperature measurement and asthma control in children prescribed inhaled corticosteroids: A cross sectional study

BACKGROUND: Exhaled breath temperature (EBT) reflects airways (both eosinophilic and neutrophilic) inflammation in asthma and thus may aid the management of children with asthma that are treated with anti-inflammatory drugs. A new EBT monitor has become available that is cheap and easy to use and may be a suitable monitoring device for airways inflammation. Little is known about how EBT relates to asthma treatment decisions, disease control, lung function, or other non-invasive measures of airways inflammation, such as exhaled nitric oxide (ENO).

OBJECTIVE: To determine the relationships between EBT and asthma treatment decision, current control, pulmonary function, and ENO.

METHODS: Cross-sectional prospective study on 159 children aged 5-16 years attending a pediatric respiratory clinic. EBT was compared with the clinician's decision regarding treatment (decrease, no change, increase), asthma control assessment (controlled, partial, uncontrolled), level of current treatment (according to British Thoracic Society guideline, BTS step), ENO, and spirometry.

RESULTS: EBT measurement was feasible in the majority of children (25 of 159 could not perform the test) and correlated weakly with age (R = 0.33, P = <0.01). EBT did not differ significantly between the three clinician decision groups (P = 0.42), the three asthma control assessment groups (P = 0.9), or the current asthma treatment BTS step (P = 0.57).

CONCLUSIONS & CLINICAL IMPLICATIONS: EBT measurement was not related to measures of asthma control determined at the clinic. The routine intermittent monitoring of EBT in children prescribed inhaled corticosteroids who attend asthma clinics cannot be recommended for adjusting anti-inflammatory asthma therapy.

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. 

Motor deficits in children with autism spectrum disorder: A cross-syndrome study

Recent research suggests that children with autism spectrum disorder (ASD) experience some level of motor difficulty, and that this may be associated with social communication skills. However, other studies show that children with language impairments, but without the social communication problems, are at risk of motor difficulties as well. The aim of the present study was to determine if children with ASD have syndrome specific motor deficits in comparison to children with specific language impairment (SLI). We used an independent groups design with three groups of children (8-10 years old) matched on age and nonverbal IQ; an ASD group, an SLI group, and a typically developing (TD) group. All of the children completed an individually administered, standardized motor assessment battery. We found that the TD group demonstrated significantly better motor skills than either the ASD or SLI groups. Detailed analyses of the motor subtests revealed that the ASD and SLI groups had very similar motor profiles across a range of fine and gross motor skills, with one exception. We conclude that children with ASD, and SLI, are at risk of clinically significant motor deficits. However, future behavioural and neurological studies of motor skills in children with ASD should include an SLI comparison group in order to identify possible autism specific deficits.

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.

Shortened Lung Clearance Index is a repeatable and sensitive test in children and adults with cystic fibrosis

Background: Lung clearance index (LCI) derived from sulfur hexafluoride (SF6) multiple breath washout (MBW) is a sensitive measure of lung disease in people with cystic fibrosis (CF). However, it can be time-consuming, limiting its use clinically. Aim: To compare the repeatability, sensitivity and test duration of LCI derived from washout to 1/30th (LCI1/30), 1/20th (LCI1/20) and 1/10th (LCI1/10) to ‘standard’ LCI derived from washout to 1/40th initial concentration (LCI1/40). Methods: Triplicate MBW test results from 30 clinically stable people with CF and 30 healthy controls were analysed retrospectively. MBW tests were performed using 0.2% SF6 and a modified Innocor device. All LCI end points were calculated using SimpleWashout software. Repeatability was assessed using coefficient of variation (CV%). The proportion of people with CF with and without abnormal LCI and forced expiratory volume in 1 s (FEV1) % predicted was compared. Receiver operating characteristic (ROC) curve statistics were calculated. Test duration of all LCI end points was compared using paired t tests. Results: In people with CF, LCI1/40 CV% (p=0.16), LCI1/30 CV%, (p=0.53), LCI1/20 CV% (p=0.14) and LCI1/10 CV% (p=0.25) was not significantly different to controls. The sensitivity of LCI1/40, LCI1/30 and LCI1/20 to the presence of CF was equal (67%). The sensitivity of LCI1/10 and FEV1% predicted was lower (53% and 47% respectively). Area under the ROC curve (95% CI) for LCI1/40, LCI1/30, LCI1/20, LCI1/10 and FEV1% predicted was 0.89 (0.80 to 0.97), 0.87 (0.77 to 0.96), 0.87 (0.78 to 0.96), 0.83 (0.72 to 0.94) and 0.73 (0.60 to 0.86), respectively. Test duration of LCI1/30, LCI1/20 and LCI1/10 was significantly shorter compared with the test duration of LCI1/40 in people with CF (p<0.0001) equating to a 5%, 9% and 15% time saving, respectively. Conclusions: In this study, LCI1/20 was a repeatable and sensitive measure with equal diagnostic performance to LCI1/40. LCI1/20 was shorter, potentially offering a more feasible research and clinical measure.

The effects of sevoflurane and ketamine on intraocular pressure in children during examination under anesthesia

PURPOSE: We studied the effects on intraocular pressure (IOP) of anesthesia administered during examination under anesthesia (EUA) in children. DESIGN: Randomized clinical trial. METHODS: This randomized trial compared IOP after inhaled sevoflurane gas to that after intramuscular ketamine hydrochloride in children undergoing EUA. IOP was measured in 30 eyes with TonoPen XL (Mentor, Inc, Norwell, Massachusetts, USA) as soon as possible after anesthesia induction (T1) and two, four, six, and eight minutes thereafter. At the same times, we recorded systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR). RESULTS: Compared with the mean IOP at T1, IOP in the sevoflurane group was significantly lower for all measurements from two to eight minutes thereafter (mean decrease in IOP: two minutes = 12%, four minutes = 19%; six minutes = 19%; eight minutes = 17%, all P < or = .01). In the ketamine group, mean IOP was not significantly changed from T1 through six minutes, whereas at eight minutes, it was 7% lower (P = .03). SBP and DBP were significantly lower for sevoflurane than for ketamine at all measurements from two minutes onward, and HR was lower for sevoflurane than for ketamine at two, four, and six minutes. CONCLUSIONS: IOP measured after ketamine sedation is more likely to represent the awake IOP than that after sevoflurane anesthesia. Changes in SBP, DBP, and HR caused by sevoflurane suggest that hemodynamic alterations may underlie its effects on IOP.