Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study.

OBJECTIVES: Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5-16 years over 13 months. SECONDARY OBJECTIVES: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis. DESIGN: Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5-16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term). PARTICIPANTS: Patients 5-16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland. OUTCOME MEASURES: Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests. RESULTS: 285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years. CONCLUSIONS: Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people.

Recovery from chronic fatigue syndrome: a systematic review-heterogeneity of definition limits study comparison.

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a common illness with a major impact on quality of life. Recovery is poorly understood. Our aim was to describe definitions of recovery in paediatric CFS/ME, the rate of recovery and the time to recovery. METHODS: This systematic review included a detailed search of MEDLINE, EMBASE, PsycInfo and Cochrane Library between 1994 and July 2018. Inclusion criteria were (1) clinical trials and observational studies, (2) participants aged <19 years with CFS/ME, (3) conducted in Western Healthcare systems and (4) studies including a measure of recovery and time taken to recover. RESULTS: Twelve papers (10 studies) were identified, involving 826 patients (range 23-135). Recovery rates were highly varied, ranging between 4.5% and 83%.Eleven distinct definitions of recovery were used; six were composite outcomes while five used unidimensional outcomes. Outcome measures used to define recovery were highly heterogeneous. School attendance (n=8), fatigue (n=6) and physical functioning (n=4) were the most common outcomes included in definition of recovery. Only five definitions included a personal measure of recovery. IMPLICATIONS: Definitions of recovery are highly variable, likely secondary to differences in study design, outcomes used, follow-up and study populations. Heterogeneous definitions of recovery limit meaningful comparison between studies, highlighting the need for a consensus definition going forward. Recovery is probably best defined from the child's own perspective with a single self-reported measure. If composite measures are used for research, there should be agreement on the core outcome set used.

CONservative TReatment of Appendicitis in Children: a randomised controlled feasibility Trial (CONTRACT).

OBJECTIVE: To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis. DESIGN: Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial. SETTING: Three specialist paediatric surgery centres in the UK. PATIENTS: Children (aged 4-15 years) with a clinical diagnosis of uncomplicated acute appendicitis. INTERVENTIONS: Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation). MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course. RESULTS: Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable. CONCLUSION: Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible. TRIAL REGISTRATION NUMBER: ISRCTN15830435.

Enhancing communication, informed consent and recruitment in a paediatric urgent care surgical trial: a qualitative study.

BACKGROUND: Recruiting patients to paediatric trials can be challenging, especially in trials that compare markedly different management pathways and are conducted in acute settings. We aimed to enhance informed consent and recruitment in the CONTRACT trial (CONservative TReatment of Appendicitis in Children a randomised controlled Trial; ISRCTN15830435) - a feasibility trial that compared non-operative treatment (antibiotics) versus appendicectomy for uncomplicated acute appendicitis. METHODS: Qualitative study embedded within CONTRACT and conducted across three UK children's hospitals. Data were transcribed audio-recordings of 85 CONTRACT recruitment consultations with 58 families; and semi-structured interviews with 35 health professionals and 28 families (34 parents, 14 children) invited to participate in CONTRACT. Data analysis drew on thematic approaches. Throughout CONTRACT, we used findings from the ongoing qualitative analysis to inform bespoke communication training for health professionals recruiting to CONTRACT. Before and after training we also examined qualitative changes in communication during consultations and quantitative changes in recruitment rates. RESULTS: Bespoke communication training focussed on presenting the trial arms in a balanced way, emphasising clinical equipoise, exploring family treatment preferences and managing families' expectations about the trial's treatment pathways. Analysis of recruitment consultations indicated that health professionals' presentation of treatment arms became increasingly balanced following training, (e.g. avoiding imbalanced terminology) and recruitment rose from 38 to 62%. However, they remained reluctant to explore families' treatment preferences and respond with further information to balance these preferences. Analyses of interviews identified the time constraints of the urgent care setting, concerns about coercion, and reservations about exposing children to conversations about treatment risks as reasons for this reluctance. Interviews with families indicated the importance of clear explanations of trial treatment timings and sensitive communication of treatment allocation for both recruitment and retention. CONCLUSIONS: Following bespoke training based on the qualitative analyses, health professionals presented CONTRACT to families in clearer and more balanced ways and this was associated with an increase in the recruitment rate. Despite training, health professionals remained reluctant to explore families' treatment preferences. We provide several recommendations to enhance communication, informed consent, recruitment and retention in future trials in urgent care settings.

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

BACKGROUND: Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. METHODS/DESIGN: The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery. DISCUSSION: In this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design. TRIAL REGISTRATION: ISRCTN15830435 . Registered on 8 February 2017.

Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial.

OBJECTIVE: Investigate the effectiveness and cost-effectiveness of the Lightning Process (LP) in addition to specialist medical care (SMC) compared with SMC alone, for children with chronic fatigue syndrome (CFS)/myalgic encephalitis (ME). DESIGN: Pragmatic randomised controlled open trial. Participants were randomly assigned to SMC or SMC+LP. Randomisation was minimised by age and gender. SETTING: Specialist paediatric CFS/ME service. PATIENTS: 12-18 year olds with mild/moderate CFS/ME. MAIN OUTCOME MEASURES: The primary outcome was the the 36-Item Short-Form Health Survey Physical Function Subscale (SF-36-PFS) at 6 months. Secondary outcomes included pain, anxiety, depression, school attendance and cost-effectiveness from a health service perspective at 3, 6 and 12 months. RESULTS: We recruited 100 participants, of whom 51 were randomised to SMC+LP. Data from 81 participants were analysed at 6 months. Physical function (SF-36-PFS) was better in those allocated SMC+LP (adjusted difference in means 12.5(95% CI 4.5 to 20.5), p=0.003) and this improved further at 12 months (15.1 (5.8 to 24.4), p=0.002). At 6 months, fatigue and anxiety were reduced, and at 12 months, fatigue, anxiety, depression and school attendance had improved in the SMC+LP arm. Results were similar following multiple imputation. SMC+LP was probably more cost-effective in the multiple imputation dataset (difference in means in net monetary benefit at 12 months £1474(95% CI £111 to £2836), p=0.034) but not for complete cases. CONCLUSION: The LP is effective and is probably cost-effective when provided in addition to SMC for mild/moderately affected adolescents with CFS/ME. TRIAL REGISTRATION NUMBER: ISRCTN81456207.

Obesity is a risk factor for musculoskeletal pain in adolescents: findings from a population-based cohort.

Obesity is a risk factor for fibromyalgia in adults, but whether a similar relationship exists in children is uncertain. This study examined whether obesity is associated with reporting of musculoskeletal pain, including chronic regional pain (CRP) and chronic widespread pain (CWP), in adolescents, in a population-based setting. A pain questionnaire was administered to offspring of the Avon Longitudinal Study of Parents and Children at age 17, asking about site, duration, and pain intensity, from which participants with different types of musculoskeletal pain were identified. Relationships between obesity and pain were examined by calculating odds ratios stratified by gender and adjusted for socioeconomic status as reflected by level of maternal education. A total of 3376 participants (1424 boys) with complete data were identified, mean age 17.8; 44.7% of participants reported any pain within the last month lasting 1day or longer; 16.3% reported lower back pain, 9.6% shoulder pain, 9.4% upper back pain, 8.9% neck pain, 8.7% knee pain, 6.8% ankle/foot pain, 4.7% CRP, and 4.3% CWP; 7.0% of participants were obese. Obesity was associated with increased odds of any pain (odds ratio [OR] 1.33, P=.04), CRP (OR 2.04, P=.005), and knee pain (OR 1.87, P=.001), but not CWP (OR 1.10, P=.5). Compared with non obese participants, those with any pain, knee pain, and CRP reported more severe average pain (P<.01). Obese adolescents were more likely to report musculoskeletal pain, including knee pain and CRP. Moreover, obese adolescents with knee pain and CRP had relatively high pain scores, suggesting a more severe phenotype with worse prognosis.