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      Understanding the role of the immune system in adolescent idiopathic scoliosis: Immunometabolic CONnections to Scoliosis (ICONS) study protocol

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          Abstract

          Introduction

          Adolescent idiopathic scoliosis (AIS) affects up to 3% of children around the world. There is limited knowledge of AIS aetiopathogenesis, and this evidence is needed to develop new management strategies. Paraspinal muscle in AIS demonstrates evidence of differential fibrosis based on curve sidedness. Fibrosis is the hallmark of macrophage-driven inflammation and tissue remodelling, yet the mechanisms of fibrosis in paraspinal muscle in AIS are poorly understood.

          Objectives

          The primary objective of this study is to determine the influence of curve sidedness on paraspinal muscle inflammation. Secondary objectives include defining the mechanisms of macrophage homing to muscle, and determining muscle–macrophage crosstalk in muscle fibrosis in AIS.

          Methods and analysis

          This is a cross-sectional study conducted in a tertiary paediatric centre in Hamilton, Ontario, Canada. We will recruit boys and girls, 10–17 years of age, who are having surgery to correct AIS. We will exclude children who have an active infection or are on immunosuppressive therapies within 2 weeks of surgery, smokers and pregnant girls. Paraspinal muscle biopsies will be obtained at the start of surgery. Also, blood and urine samples will be collected from participants, who will fill questionnaires about their lifestyle. Anthropometric measures will also be collected including height, weight, waist and hip circumferences.

          Ethics and dissemination

          This study has received ethics authorisation by the institutional review board. This work will be published in peer-reviewed journals and will be presented in oral and poster formats at scientific meetings.

          Discussion

          This study will explore the mechanisms of paraspinal muscle inflammation, remodelling and fibrosis in AIS. This will help identify pathways and molecules as potential therapeutic targets to treat and prevent AIS. It may also yield markers that predict scoliosis progression and response to treatment in these children.

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          Most cited references125

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          Effects of bracing in adolescents with idiopathic scoliosis.

          The role of bracing in patients with adolescent idiopathic scoliosis who are at risk for curve progression and eventual surgery is controversial. We conducted a multicenter study that included patients with typical indications for bracing due to their age, skeletal immaturity, and degree of scoliosis. Both a randomized cohort and a preference cohort were enrolled. Of 242 patients included in the analysis, 116 were randomly assigned to bracing or observation, and 126 chose between bracing and observation. Patients in the bracing group were instructed to wear the brace at least 18 hours per day. The primary outcomes were curve progression to 50 degrees or more (treatment failure) and skeletal maturity without this degree of curve progression (treatment success). The trial was stopped early owing to the efficacy of bracing. In an analysis that included both the randomized and preference cohorts, the rate of treatment success was 72% after bracing, as compared with 48% after observation (propensity-score-adjusted odds ratio for treatment success, 1.93; 95% confidence interval [CI], 1.08 to 3.46). In the intention-to-treat analysis, the rate of treatment success was 75% among patients randomly assigned to bracing, as compared with 42% among those randomly assigned to observation (odds ratio, 4.11; 95% CI, 1.85 to 9.16). There was a significant positive association between hours of brace wear and rate of treatment success (P<0.001). Bracing significantly decreased the progression of high-risk curves to the threshold for surgery in patients with adolescent idiopathic scoliosis. The benefit increased with longer hours of brace wear. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and others; BRAIST ClinicalTrials.gov number, NCT00448448.).
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            Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems.

            Objective: To develop and validate questionnaire scales that can be used in research to investigate the presence of childhood SRBDs and prominent symptom complexes, including snoring, daytime sleepiness, and related behavioral disturbances.Background: Obstructive sleep-related breathing disorders (SRBDs) are common but usually undiagnosed among children. Methods to help identify SRBDs without the expense of polysomnography could greatly facilitate clinical and epidemiological research.Methods: Subjects were children aged 2-18 years who had polysomnographically-confirmed SRBDs (n=54) or appointments at either of two general pediatrics clinics (n=108). Parents completed a Pediatric Sleep Questionnaire which contained items under consideration for inclusion in desired scales.Results: Item reduction, based on data from a randomly selected 50% of the subjects (group A), produced a 22-item SRBD score that was strongly associated with diagnosis of an SRBD (P<0.0001) in a logistic regression model that accounted for age and gender. Diagnosis was also strongly associated with subscores for snoring (four items, P<0.0001), sleepiness (four items, P=0.0003), and behavior (six items, P<0.0001) among group A subjects. The scales performed similarly well among group B subjects, and among subjects of different ages and gender. In group A and B subjects, respectively, a selected criterion SRBD score produced a sensitivity of 0.85 and 0.81; a specificity of 0.87 and 0.87; and a correct classification for 86 and 85% of subjects. The scales showed good internal consistency and, in a separate sample (n=21), good test-retest stability.Conclusions: These scales for childhood SRBDs, snoring, sleepiness, and behavior are valid and reliable instruments that can be used to identify SRBDs or associated symptom-constructs in clinical research when polysomnography is not feasible.
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              Validation of a youth/adolescent food frequency questionnaire.

              To address limited longitudinal nutrition data on children and adolescents, a self-administered food frequency questionnaire was designed for older children and adolescents. Initially, the Youth/Adolescent Questionnaire (YAQ) was developed and demonstrated to be reproducible. This study was conducted to evaluate its validity. The form was administered twice to a sample of 261 youths (ages 9 to 18) at an approximate interval of 1 year (1993-1994), and three 24-hr dietary recalls were collected during this period. Pearson correlation coefficients were calculated on nutrient data. Validity was first evaluated by comparing the average of the three 24-hr recalls to the average of the two YAQs. Similar mean nutrients were found by both methods. Correlation coefficients between the mean energy-adjusted nutrients computed by the two methods ranged from 0.21 for sodium to 0.58 for folate. After correction for within-person error, the average correlation coefficient was 0.54, similar to that found among adults. A simple self-administered questionnaire completed by older children and adolescents can provide nutritional information about this age group.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2016
                8 July 2016
                : 6
                : 7
                : e011812
                Affiliations
                [1 ]Department of Pediatrics, McMaster University , Hamilton, Ontario, Canada
                [2 ]Division of Pediatric Endocrinology, McMaster Children's Hospital , Hamilton, Ontario, Canada
                [3 ]Department of Clinical Epidemiology & Biostatistics, McMaster University , Hamilton, Ontario, Canada
                [4 ]Division of Orthopedics, Department of Surgery, McMaster University , Hamilton, Ontario, Canada
                [5 ]Department of Anesthesia, McMaster University , Hamilton, Ontario, Canada
                [6 ]Centre for Evaluation of Medicines , Hamilton, Ontario, Canada
                [7 ]Biostatistics unit, St Joseph's Healthcare Hamilton , Hamilton, Ontario, Canada
                Author notes
                [Correspondence to ] Dr M Constantine Samaan; samaanc@ 123456mcmaster.ca
                Article
                bmjopen-2016-011812
                10.1136/bmjopen-2016-011812
                4947809
                27401365
                f42c313d-5d12-40c2-b894-8e595cd46e7c
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 8 March 2016
                : 1 May 2016
                : 12 May 2016
                Categories
                Patient-Centred Medicine
                Protocol
                1506
                1722
                1719

                Medicine
                Medicine

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