Heliyon

Purpose: Restraint is often used when administering procedures to children. However, no metrologically scale to measure the restraint intensity had yet been validated. This study validated the metrological criteria of a scale measuring the restraint intensity, Procedural Restraint Intensity in Children (PRIC), used during procedures in children. Design and methods: The PRIC scale performance was measured by a group of 7 health professionals working in a children's hospital, by watching 20 videos of health care procedures. This group included 2 physicians, 1 pediatric resident, and 4 nurses. The intra-class correlation coefficients were calculated to evaluate the inter-rater and test-retest reliability and the construct validity with the correlation between PRIC scale and a numerical rating scale. Results: One hundred and forty measurements were made. Inter-rater and test-retest correlation coefficients were 0.98 and 0.98, respectively. The 2 scales were positively correlated with a Spearman coefficient of 0.93. Conclusions: This study validated the Procedural Restraint Intensity in Children (PRIC) scale in metrological terms with some limitation. However, there is not gold standard scale to precisely validate the reliability of this tool and this study has been conducted in "experimental" conditions. Nevertheless, this is the first scale measuring the intensity of physical restraint with a metrological validation. The next step will be to validate it in real clinical situations

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - Evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: Study protocol for a randomized controlled trial

Background: Gabapentin has shown efficacy in the treatment of chronic neuropathic or mixed pain in adults. Although pediatric pain specialists have extensive experience with gabapentin for the treatment of neuropathic pain, its use is off-label. Its efficacy and safety in this context have never been shown. The aim of this trial is to compare gabapentin with placebo as add-on to morphine for the treatment of severe chronic mixed or neuropathic pain in children. This trial is part of the European Union Seventh Framework Programme project Gabapentin in Paediatric Pain (GAPP) to develop a pediatric use marketing authorization for a new gabapentin suspension. Methods/design: The GAPP-2 study is a randomized, double-blind, placebo-controlled, multicenter superiority phase II study in children with severe chronic neuropathic or mixed pain. Its primary objective is to evaluate the efficacy of a gabapentin liquid formulation as adjunctive therapy to morphine. Sixty-six eligible children 3 months to 18 years of age with severe pain (pain scores ≥ 7), stratified in three age groups, will be randomized to receive gabapentin (to an accumulating dose of 45 to 63 mg/kg/day, dependent on age) or placebo, both in addition to morphine, for 12 weeks. Randomization will be preceded by a short washout period, and treatment will be initiated by a titration period of 3 weeks. After the treatment period, medication will be tapered during 4 weeks. The primary endpoint is the average pain scores in the two treatment groups (average of two measures each day for 3 days before the end-of-study visit [V10] assessed by age-appropriate pain scales (Face, Legs, Activity, Cry, Consolability scale; Faces Pain Scale-Revised; Numeric Rating Scale). Secondary outcomes include percentage responders to treatment (subjects with 30% reduction in pain scale), number of episodes of breakthrough pain, number of rescue interventions, number of pain-free days, participant dropouts, quality of life (Pediatric Quality of Life Inventory), and acceptability of treatment. Outcomes will be measured at the end-of-study visit after 12 weeks of treatment at the optimal gabapentin dose. Groups will be compared on an intention-to-treat basis. Discussion: We hope to provide evidence that the combination of morphine and gabapentin will provide better analgesia than morphine alone and will be safe. We also aim to obtain confirmation of the recommended pediatric dose. Trial registration: EudractCT, 2014-004897-40. Registered on 7 September 2017. ClinicalTrials.gov, NCT03275012. Registered on 7 September 2017

The research gap in chronic paediatric pain: A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases

Pathway Enrichment Based on Text Mining and Its Validation on Carotenoid and Vitamin A Metabolism

Abstract Carotenoid metabolism is relevant to the prevention of various diseases. Although the main actors in this metabolic pathway are known, our understanding of the pathway is still incomplete. The information on the carotenoids is scattered in the large and growing body of scientific literature. We designed a text-mining work flow to enrich existing pathways. It has been validated on the vitamin A pathway, which is a well-studied part of the carotenoid metabolism. In this study we used the vitamin A metabolism pathway as it has been described by an expert team on carotenoid metabolism from the European network of excellence in Nutrigenomics (NuGO). This work flow uses an initial set of publications cited in a review paper (1,191 publications), enlarges this corpus with Medline abstracts (13,579 documents), and then extracts the key terminology from all relevant publications. Domain experts validated the intermediate and final results of our text-mining work flow. With our approach we were able to enrich the pathway representing vitamin A metabolism. We found 37 new and relevant terms from a total of 89,086 terms, which have been qualified for inclusion in the analyzed pathway. These 37 terms have been assessed manually and as a result 13 new terms were then added as entities to the pathway. Another 14 entities belonged to other pathways, which could form the link of these pathways with the vitamin A pathway. The remaining 10 terms were classified as biomarkers or nutrients. Automatic literature analysis improves the enrichment of pathways with entities already described in the scientific literature

Longitudinal study shows that depression in childhood is associated with a worse evolution of headaches in adolescence

The aim of this study was to examine the course of headache diagnosis, headache frequency, anxiety, comorbid depressive symptoms and school absenteeism in adolescents with migraine and tension-type headaches five years after baseline. We followed a group of 122 children with a mean age of 10.1 (±1.3) years, with headache from a paediatric migraine centre in Paris who had taken part in a previous study from September 2007 to June 2008. This five-year longitudinal study took place in January to June 2012. The measures that were used included demographic variables, headache diagnosis, headache data and a psychological assessment. At the five-year point, about 22% of the children had become headache free, 34% had little to no disability, and 36% had a changed diagnosis. Moreover, a longer history of headache at baseline was associated with a worse evolution of headache at follow-up. Lastly, high depression scores, but not anxiety, were a predictor of more headache disability at follow-up. High depression scores in childhood were a risk factor that was associated with persistence and worsening of headaches in adolescence. This suggests that mental health assessments should be carried out in paediatric headache pain clinics

Shape-Invariant Modeling of Circadian Rhythms with Random Effects and Smoothing Spline ANOVA Decompositions

Medical studies often collect physiological and/or psychological measurements over time from multiple subjects, to study dynamics such as circadian rhythms. Under the assumption that the expected response functions of all subjects are the same after shift and scale transformations, shape- invariant models have been applied to analyze this kind of data. The shift and scale parameters provide efficient and interpretable data summaries, while the common shape function is usually modeled nonparametrically, to provide flexibility. However, due to the deterministic nature of the shift and scale parameters, potential correlations within a subject are ignored. Furthermore, the shape of the common function may depend on other factors, such as disease. In this article, we propose shape-invariant mixed effects models. A second-stage model with fixed and random effects is used to model individual shift and scale parameters. A second-stage smoothing spline ANOVA model is used to study potential covariate effects on the common shape function. We apply our methods to a real data set to investigate disease effects on circadian rhythms of cortisol, a hormone that is affected by stress. We find that patients with Cushing's syndrome lost circadian rhythms and their 24-hour means were elevated to very high levels. Patients with major depression had the same circadian shape and phases as normal subjects. However, their 24-hour mean levels were elevated and amplitudes were dampened for some patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66227/1/j.0006-341X.2003.00094.x.pd

Anxiety, depression and school absenteeism in youth with chronic or episodic headache.

BACKGROUND: Chronic daily headache (CDH) in children has been documented in general and clinical populations. Comorbid psychological conditions, risk factors and functional outcomes of CDH in children are not well understood. OBJECTIVES: To examine anxiety and depression, associated risk factors and school outcomes in a clinical population of youth with CDH compared with youth with episodic headache (EH). METHODS: Data regarding headache characteristics, anxiety, depression and missed school days were collected from 368 consecutive patients eight to 17 years of age, who presented with primary headache at a specialized pediatric headache centre. RESULTS: A total of 297 patients (81%) were diagnosed with EH and 71 were diagnosed with CDH. Among those with CDH, 78.9% presented with chronic tension-type headache and 21.1% with chronic migraine (CM). Children with CDH had a higher depression score than the standardized reference population. No difference was observed for anxiety or depression scores between children with CDH and those with EH. However, children with CM were more anxious and more depressed than those with chronic tension-type headache. Youth experiencing migraine with aura were three times as likely to have clinically significant anxiety scores. Headache frequency and history were not associated with psychopathological symptoms. Children with CDH missed school more often and for longer periods of time. CONCLUSIONS: These findings document the prevalence of anxiety, depression and school absenteeism in youth with CDH or EH. The present research also extends recent studies examining the impact of aura on psychiatric comorbidity and the debate on CM criteria