Lengthening sleep reduces pain in childhood arthritis: a crossover randomised controlled trial.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a common chronic childhood disease and chronic pain is a debilitating feature. A strong link has been shown between poor sleep and pain in JIA. However, the causal direction is unknown. This study's aim was to determine if, in adolescents with JIA, a recommended healthful sleep duration leads to reductions in pain when compared with the restricted sleep (RS) duration that is commonly seen. METHODS: Patients with JIA (12-18 years old; pain score of ≥1 on a visual analogue scale) participated in a randomised, crossover sleep manipulation protocol. The 3-week protocol comprised a baseline week (BL), a week with healthy sleep duration (HSD; 9.5 hours in bed/night) and a RS week (RS; 6.5 hours in bed/night). After BL, participants were randomly assigned to either HSD or RS, and then crossed over to the other condition. Pain was self-assessed using the iCanCope with Pain app. We used Bayesian hierarchical models to estimate the effect of sleep duration on pain. RESULTS: Participants (n=31; mean age=15.0±1.8 years) averaged 1.4 (95% credible interval (CrI) 1.2-1.6) more hours of sleep per night during HSD relative to RS. Compared with RS, HSD resulted in a favourable effect on pain scores (OR 0.61, 95% CrI 0.39-0.95). CONCLUSION: It is possible to have adolescents with childhood arthritis get a healthier sleep duration, and this longer sleep results in reduced pain. These findings complement prior correlational studies and confirm a causal relationship between reduced sleep duration and increased pain. TRIAL REGISTRATION NUMBER: NCT04133662.

Feasibility of the wingate anaerobic exercise test as a clinical measure in patients with juvenile dermatomyositis.

BACKGROUND: Core sets, while widely adopted for clinical assessment in juvenile dermatomyositis (JDM), have some drawbacks - they are time consuming, were developed primarily for research, and require an experienced multidisciplinary team. We propose the Wingate Anaerobic Test, a 30-s all out test performed on a cycle ergometer, as a potential alternative; it is valid and reliable in this patient population. We aimed to determine the feasibility of performing the Wingate test as part of a typical clinic visit, and to determine if it is correlated to current measures of disease activity. METHODS: Patients 5-18 years of age, with JDM, were recruited from the JDM clinic at a large Canadian academic children's hospital. Participants underwent a standard clinic assessment, then completed a Wingate test at the end of the visit. RESULTS: Twenty-six patients participated in the study, representing a recruitment rate of 81%; of those, 88% were able to complete the Wingate test. Patients liked the Wingate test and felt it should be included as a regular clinic test. Absolute peak power (watts) on the Wingate test was strongly correlated to the manual muscle test (MMT-8) and the timed squat test. Relative peak power (watts/kg) on the Wingate test was strongly correlated to the timed squat test and the Childhood Myositis Assessment Scale (CMAS). Exploratory principal components analysis revealed that Wingate relative average power explained almost 2/3 of the variance of the CMAS, MMT and timed squats combined. CONCLUSION: The Wingate test is a feasible test for children with JDM and correlates well with standard clinical assessments. Given its brevity, it has the potential to replace more standard measures of physical function currently used in clinical assessments for children with JDM. Future work should focus on how best to operationalize Wingate testing in clinic without the use of dedicated personnel.

Correlation of a Modified Disease Activity Score (DAS) with the Validated Original DAS in Patients with Juvenile Dermatomyositis.

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare disease in children that is treatable, but patients may suffer from long-term effects. Clinical trials are needed to find better treatments for affected patients. Among validated tools for evaluating disease activity clinically is the Disease Activity Score (DAS), but it is not routinely collected in all clinics. We developed a modified DAS (DASmod), which can be scored using data routinely collected by our clinical staff and has been used in previous studies. The aim of this study was to determine if our DASmod correlates with the validated DAS in patients with JDM. METHODS: In this study, we used DASmod (scored 0-12) and DAS (scored 0-20) scores for patients with JDM in our clinic. We analyzed the correlation between the DASmod and the validated DAS. RESULTS: For 51 patients seen in our JDM clinic, the median (IQR) DASmod score was 2.0 (0-4.0) and the DAS score was 3.0 (0-5.5). Scores on the 2 tools were highly positively correlated (r = 0.94, P < 0.001, 95% CI 0.89-0.96). The linear regression was significant [R2 = 0.88, F (1, 49) = 357.60, P < 0.001] and in this dataset, the tools can be used interchangeably with the regression equation: DAS score = -0.26 + 1.5*DASmod. CONCLUSION: If the regression equation from this dataset is successfully tested against future datasets, then further research collaborations between centers that collect different data related to disease activity in children with JDM will be facilitated.

Establishing an Updated Core Domain Set for Studies in Juvenile Idiopathic Arthritis: A Report from the OMERACT 2018 JIA Workshop.

OBJECTIVE: The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting. METHODS: Candidate domains were identified through literature review, qualitative surveys, and online discussion boards (ODB) held with patients with JIA and parents in Australia, Italy, and the United States. A Delphi process with parents, patients, healthcare providers, researchers, and regulators served to edit the domain list and prioritize candidate domains. After the presentation of results, OMERACT workshop participants voted, with consensus set at > 70%. RESULTS: Participants in ODB were 53 patients with JIA (ages 15-24 yrs) and 55 parents. Three rounds of Delphi considering 27 domains were completed by 190 (response rate 85%), 201 (84%), and 182 (77%) people, respectively, from 50 countries. There was discordance noted between domains prioritized by patients/parents compared to others. OMERACT conference voting approved domains for JIA RCT and LOS with 83% endorsement. Mandatory domains are pain, joint inflammatory signs, activity limitation/physical function, patient's perception of disease activity (overall well-being), and adverse events. Mandatory in specific circumstances: inflammation/other features relevant to specific JIA categories. CONCLUSION: Following the OMERACT methodology, we developed an updated JIA Core Domain Set. Next steps are to identify and systematically evaluate best outcome measures for these domains.

Publisher Correction: Pathways to eating in children and adolescents with obesity.

In the original version of this Article the following were listed as authors; however, they should have only been referred to in the Acknowledgments section and not listed in this way.

Pathways to eating in children and adolescents with obesity.

BACKGROUND: Paediatric obesity management remains generalised to dietary and exercise modifications with an underappreciation for the contributions of eating behaviours and appetitive traits in the development of obesity. OBJECTIVES: To determine whether treatment-seeking children and adolescents with obesity cluster into phenotypes based on known eating behaviours and appetitive traits ("eating correlates") and how socio-demographic and clinical characteristics associate with different phenotypes. METHODS: A cross-sectional, multi-centre questionnaire was administered between November 2015 and March 2017 examining correlates of eating in children and adolescents attending weight-management programmes in Canada. Latent profile analysis was used to cluster participants based on seven eating correlate scores obtained from questionnaires. Analysis of variance (ANOVA) was used to determine phenotype differences on socio-demographic and clinical characteristics. Multinomial logistic regression models assessed relative risk of specific characteristics associating with a disordered eating phenotype. RESULTS: Participants were 247 children and adolescents (45.3% male, mean BMI z-score = 3.4 ± 1.0 kg/m2) from six paediatric weight management centres in Canada. Seven eating correlates clustered into three distinct phenotypes: (1) loss of control eating, emotional eating, external eating, hyperphagia, impulsivity ("Mixed-Severe"; n = 42, 17%), (2) loss of control eating, emotional eating, external eating, hyperphagia ("Mixed-Moderate"; n = 138, 55.9%), and (3) impulsivity ("Impulsive"; n = 67; 27.1%). Social functioning scores and body esteem were significantly different across groups, with the Mixed-Severe participants having the poorest social functioning and lowest body esteem. Low body esteem indicated a greater risk of being in a multi-correlate group compared to the Impulsive group, while poor social function had a greater risk of clustering in the Mixed-Severe than Impulsive phenotype. CONCLUSIONS: Distinct eating phenotypes were found in treatment-seeking children and adolescents with obesity. Empirical evidence is needed, but these data suggest that tailored treatment approaches could be informed by these classifications to improve weight-management outcomes.

Preliminary Findings that a Targeted Intervention Leads to Altered Brain Function in Children with Fetal Alcohol Spectrum Disorder.

Children with fetal alcohol spectrum disorder (FASD) exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral regulation and executive function in children with FASD, we asked if this therapy also improves their neural functioning in associated regions. Twenty-one children with FASD aged 8-12 years were randomized to the Alert®-treatment (TXT; n = 10) or waitlist-control (WL; n = 11) conditions. They were assessed with a Go-NoGo functional magnetic resonance imaging (fMRI) paradigm before and after training or the wait-out period. Groups initially performed equivalently and showed no fMRI differences. At post-test, TXT outperformed WL on NoGo trials while fMRI in uncorrected results with a small-volume correction showed less activation in prefrontal, temporal, and cingulate regions. Groups also demonstrated different patterns of change over time reflecting reduced signal at post-test in selective prefrontal and parietal regions in TXT and increased in WL. In light of previous evidence indicating TXT at post-test perform similar to non-exposed children on the Go-NoGo fMRI paradigm, our findings suggest Alert® does improve functional integrity in the neural circuitry for behavioral regulation in children with FASD.

Parent Preferences for Medical Error Disclosure: A Qualitative Study.

OBJECTIVE: According to disclosure guidelines, patients experiencing adverse events due to medical errors should be offered full disclosure, whereas disclosure of near misses is not traditionally expected. This may conflict with parental expectations; surveys reveal most parents expect full disclosure whether errors resulted in harm or not. Protocols regarding whether to include children in these discussions have not been established. This study explores parent preferences around disclosure and views on including children. METHODS: Fifteen parents of hospitalized children participated in semistructured interviews. Three hypothetical scenarios of different severity were used to initiate discussion. Interviews were audiotaped, transcribed, and coded for emergent themes. RESULTS: Parents uniformly wanted disclosure if harm occurred, although fewer wanted their child informed. For nonharmful errors, most parents wanted disclosure for themselves but few for their children.With respect to including children in disclosure, parents preferred to assess their children's cognitive and emotional readiness to cope with disclosure, wishing to act as a "buffer" between the health care team and their children. Generally, as event severity decreased, they felt that risks of informing children outweighed benefits. Parents strongly emphasized needing reassurance of a good final outcome and anticipated difficulty managing their emotions. CONCLUSIONS: Parents have mixed expectations regarding disclosure. Although survey studies indicate a stronger desire for disclosure of nonharmful events than for adult patients, this qualitative study revealed a greater degree of hesitation and complexity. Parents have a great need for reassurance and consistently wish to act as a buffer between the health care team and their children.

[Formula: see text]Social perception in children with fetal alcohol spectrum disorder.

Although the profile of social cognitive difficulties is well recognized in children with certain neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), this profile is not as well established in other clinical pediatric populations. The objective of the present study is to examine patterns of social perception in children with fetal alcohol spectrum disorder (FASD) compared to typically-developing (TD) control children. A total of 56 children between 8 and 12 years of age-35 with FASD and 21 TD-completed the Reading the Mind in the Eyes Task - Children's Version (RMET-C). The RMET-C accuracy scores were compared between groups and also by item difficulty and emotional valence. The relation between cognitive functioning, age, FASD severity, and RMET-C performance was also investigated. The children in the FASD group did not perform as well as the children in the TD group on the RMET-C Total score and Easy items, as well as the Positive, Negative, and Neutral emotional valence items. When age and IQ were investigated, there was a significant effect of age on the Positive items in the TD group, with scores increasing with age. With regard to FASD severity, children with alcohol-related neurodevelopmental disorder were outperformed by children with full/partial fetal alcohol syndrome on the Positive and Negative items. Overall, these results further the understanding of the social cognitive profile in children with FASD and how this profile relates to other childhood-onset neurodevelopmental disorders.

Preliminary Findings Show Maternal Hypothyroidism May Contribute to Abnormal Cortical Morphology in Offspring.

In rodents, insufficient thyroid hormone (TH) gestationally has adverse effects on cerebral cortex development. Comparable studies of humans examining how TH insufficiency affects cortical morphology are limited to children with congenital hypothyroidism or offspring of hypothyroxinemic women; effects on cortex of children born to women with clinically diagnosed hypothyroidism are not known. We studied archived MRI scans from 22 children aged 10-12 years born to women treated for preexisting or de novo hypothyroidism in pregnancy (HYPO) and 24 similar age and sex controls from euthyroid women. FreeSurfer Image Analysis Suite software was used to measure cortical thickness (CT) and a vertex-based approach served to compare HYPO versus control groups and Severe versus Mild HYPO subgroups as well as to perform regression analyses examining effects of trimester-specific maternal TSH on CT. Results showed that relative to controls, HYPO had multiple regions of both cortical thinning and thickening, which differed for left and right hemispheres. In HYPO, thinning was confined to medial and mid-lateral regions of each hemisphere and thickening to superior regions (primarily frontal) of the left hemisphere and inferior regions (particularly occipital and temporal) of the right. The Severe HYPO subgroup showed more thinning than Mild in frontal and temporal regions and more thickening in bilateral posterior and frontal regions. Maternal TSH values predicted degree of thinning and thickening within multiple brain regions, with the pattern and direction of correlations differing by trimester. Notably, some correlations remained when cases born to women with severe hypothyroidism were removed from the analyses, suggesting that mild variations of maternal TH may permanently affect offspring cortex. We conclude that maternal hypothyroidism during pregnancy has long-lasting manifestations on the cortical morphology of their offspring with specific effects reflecting both severity and timing of maternal TH insufficiency.

Do children with congenital hypothyroidism exhibit abnormal cortical morphology?

BACKGROUND: Given thyroid hormone (TH)'s essential role in multiple aspects of early brain development, children with congenital hypothyroidism (CH) detected and treated early may still display subtle cognitive and behavioral impairments as well as brain abnormalities. However, effects on their cortical development are not yet known. We used an automated neuroimaging technique to determine if these children differ in cortical thickness (CT) from typically developing controls (TDC) and if the regions showing CT differences reflect severity of initial hypothyroidism and predict later neuropsychological functioning. METHODS: FreeSurfer Image Analysis Suite was used on archived MRI scans from 41 CH and 42 TDC children aged 9-16 y. Vertex-based procedures were used to compare groups and perform correlations between CT and indices of disease severity and neuropsychological outcome. RESULTS: The CH group showed multiple regions of cortical thinning or cortical thickening within right and left hemispheres relative to TDC. CT values were significantly correlated with early T4 and thyroid-stimulating hormone (TSH) levels and current neuropsychological test indices. CONCLUSION: The developing cortex is sensitive to early TH loss in CH. Different patterns of cortical thinning or cortical thickening among brain regions may reflect timing of TH deficiency relative to timing of cortical development.