Recurrent Abdominal Pain in Children: Summary Evidence From 3 Systematic Reviews of Treatment Effectiveness.

OBJECTIVES: Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. METHODS: We carried out a systematic review of randomised controlled trials (RCTs) in eleven databases and 2 trials registries from inception to June 2016. An update search was run in November 2017. All screening was performed by 2 independent reviewers. Included studies were appraised using the Cochrane risk of bias tool and the evidence assessed using GRADE. We included any dietary, pharmacological or psychosocial intervention for RAP, defined by Apley or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria, in children and adolescents. RESULTS: We included 55 RCTs, involving 3572 children with RAP (21 dietary, 15 pharmacological, 19 psychosocial, and 1 multiarm). We found probiotic diets, cognitive-behavioural therapy (CBT) and hypnotherapy were reported to reduce pain in the short-term and there is some evidence of medium term effectiveness. There was insufficient evidence of effectiveness for all other dietary interventions and psychosocial therapies. There was no robust evidence of effectiveness for pharmacological interventions. CONCLUSIONS: Overall the evidence base for treatment decisions is poor. These data suggest that probiotics, CBT, and hypnotherapy could be considered as part of holistic management of children with RAP. The evidence regarding relative effectiveness of different strains of probiotics is currently insufficient to guide clinical practice. The lack of evidence of effectiveness for any drug suggests that there is little justification for their use outside of well-conducted clinical trials. There is an urgent need for high-quality RCTs to provide evidence to guide management of this common condition.

Pharmacological interventions for recurrent abdominal pain in childhood.

BACKGROUND: Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children. OBJECTIVES: To determine the effectiveness of pharmacological interventions for RAP in children of school age. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies. SELECTION CRITERIA: Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results. MAIN RESULTS: This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies. AUTHORS' CONCLUSIONS: There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.

Dietary interventions for recurrent abdominal pain in childhood.

BACKGROUND: This is an update of the original Cochrane review, last published in 2009 (Huertas-Ceballos 2009). Recurrent abdominal pain (RAP), including children with irritable bowel syndrome, is a common problem affecting between 4% and 25% of school-aged children. For the majority of such children, no organic cause for their pain can be found on physical examination or investigation. Many dietary inventions have been suggested to improve the symptoms of RAP. These may involve either excluding ingredients from the diet or adding supplements such as fibre or probiotics. OBJECTIVES: To examine the effectiveness of dietary interventions in improving pain in children of school age with RAP. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Embase, eight other databases, and two trials registers, together with reference checking, citation searching and contact with study authors, in June 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing dietary interventions with placebo or no treatment in children aged five to 18 years with RAP or an abdominal pain-related, functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We grouped dietary interventions together by category for analysis. We contacted study authors to ask for missing information and clarification, when needed. We assessed the quality of the evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study).We found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity.We found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity.Children with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies.We found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity.We found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible.We were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them.With the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported. AUTHORS' CONCLUSIONS: Overall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome.We found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.

Psychosocial interventions for recurrent abdominal pain in childhood.

BACKGROUND: This review supersedes the original Cochrane review first published in 2008 (Huertas-Ceballos 2008).Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. No organic cause for this pain can be found on physical examination or investigation for the majority of such children. Although many children are managed by reassurance and simple measures, a large range of psychosocial interventions involving cognitive and behavioural components have been recommended. OBJECTIVES: To determine the effectiveness of psychosocial interventions for reducing pain in school-aged children with RAP. SEARCH METHODS: In June 2016 we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the references of identified studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials comparing psychosocial therapies with usual care, active control, or wait-list control for children and adolescents (aged 5 to 18 years) with RAP or an abdominal pain-related functional gastrointestinal disorder defined by the Rome III criteria were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Five review authors independently selected studies, assessed them for risk of bias, and extracted relevant data. We also assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This review includes 18 randomised controlled trials (14 new to this version), reported in 26 papers, involving 928 children and adolescents with RAP between the ages of 6 and 18 years. The interventions were classified into four types of psychosocial therapy: cognitive behavioural therapy (CBT), hypnotherapy (including guided imagery), yoga, and written self-disclosure. The studies were carried out in the USA, Australia, Canada, the Netherlands, Germany, and Brazil. The majority of the studies were small and short term; only two studies included more than 100 participants, and only five studies had follow-up assessments beyond six months. Small sample sizes and the degree of assessed risk of performance and detection bias in many studies led to the overall quality of the evidence being rated as low to very low for all outcomes.For CBT compared to control, we found evidence of treatment success postintervention (odds ratio (OR) 5.67, 95% confidence interval (CI) 1.18 to 27.32; Z = 2.16; P = 0.03; 4 studies; 175 children; very low-quality evidence), but no evidence of treatment success at medium-term follow-up (OR 3.08, 95% CI 0.93 to 10.16; Z = 1.85; P = 0.06; 3 studies; 139 children; low-quality evidence) or long-term follow-up (OR 1.29, 95% CI 0.50 to 3.33; Z = 0.53; P = 0.60; 2 studies; 120 children; low-quality evidence). We found no evidence of effects of intervention on pain intensity scores measured postintervention (standardised mean difference (SMD) -0.33, 95% CI -0.74 to 0.08; 7 studies; 405 children; low-quality evidence), or at medium-term follow-up (SMD -0.32, 95% CI -0.85 to 0.20; 4 studies; 301 children; low-quality evidence).For hypnotherapy (including studies of guided imagery) compared to control, we found evidence of greater treatment success postintervention (OR 6.78, 95% CI 2.41 to 19.07; Z = 3.63; P = 0.0003; 4 studies; 146 children; low-quality evidence) as well as reductions in pain intensity (SMD -1.01, 95% CI -1.41 to -0.61; Z = 4.97; P < 0.00001; 4 studies; 146 children; low-quality evidence) and pain frequency (SMD -1.28, 95% CI -1.84 to -0.72; Z = 4.48; P < 0.00001; 4 studies; 146 children; low-quality evidence). The only study of long-term effect reported continued benefit of hypnotherapy compared to usual care after five years, with 68% reporting treatment success compared to 20% of controls (P = 0.005).For yoga therapy compared to control, we found no evidence of effectiveness on pain intensity reduction postintervention (SMD -0.31, 95% CI -0.67 to 0.05; Z = 1.69; P = 0.09; 3 studies; 122 children; low-quality evidence).The single study of written self-disclosure therapy reported no benefit for pain.There was no evidence of effect from the pooled analyses for any type of intervention on the secondary outcomes of school performance, social or psychological functioning, and quality of daily life.There were no adverse effects for any of the interventions reported. AUTHORS' CONCLUSIONS: The data from trials to date provide some evidence for beneficial effects of CBT and hypnotherapy in reducing pain in the short term in children and adolescents presenting with RAP. There was no evidence for the effectiveness of yoga therapy or written self-disclosure therapy. There were insufficient data to explore effects of treatment by RAP subtype.Higher-quality, longer-duration trials are needed to fully investigate the effectiveness of psychosocial interventions. Identifying the active components of the interventions and establishing whether benefits are sustained in the long term are areas of priority. Future research studies would benefit from employing active control groups to help minimise potential bias from wait-list control designs and to help account for therapist and intervention time.

Non-pharmacological interventions for attention-deficit/hyperactivity disorder (ADHD) delivered in school settings: systematic reviews of quantitative and qualitative research.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by age-inappropriate levels of inattention, impulsivity and hyperactivity. School can be particularly challenging for children with ADHD. Few reviews have considered non-pharmacological interventions in school settings. OBJECTIVES: To assess the effectiveness of non-pharmacological interventions delivered in school settings for pupils with, or at risk of, ADHD and to explore the factors that may enhance, or limit, their delivery. DATA SOURCES: Twenty electronic databases (including PsycINFO, MEDLINE, EMBASE, Education Resources Information Centre, The Cochrane Library and Education Research Complete) were searched from 1980 to February-August 2013. Three separate searches were conducted for four systematic reviews; they were supplemented with forward and backwards citation chasing, website searching, author recommendations and hand-searches of key journals. REVIEW METHODS: The systematic reviews focused on (1) the effectiveness of school-based interventions for children with or at risk of ADHD; (2) quantitative research that explores attitudes towards school-based non-pharmacological interventions for pupils with ADHD; (3) qualitative research investigating the attitudes and experiences of children, teachers, parents and others using ADHD interventions in school settings; and (4) qualitative research exploring the experience of ADHD in school among pupils, their parents and teachers more generally. Methods of synthesis included a random-effects meta-analysis, meta-regression and narrative synthesis for review 1, narrative synthesis for review 2 and meta-ethnography and thematic analysis for reviews 3 and 4. RESULTS: For review 1, 54 controlled trials met the inclusion criteria. For the 36 meta-analysed randomised controlled trials, beneficial effects (p < 0.05) were observed for several symptom and scholastic outcomes. Mean weighted effect sizes ranged from very small (d + < 0.20) to large (d + ≥ 0.80), but substantial heterogeneity in effect size estimates across studies was reported. Moderator analyses were not able to clarify which intervention features were linked with effectiveness. For review 2, 28 included studies revealed that educators' attitudes towards interventions ranged in positivity. Most interventions were rated positively or neutrally across different studies. The only intervention that consistently recorded positive attitudes from educators was daily report cards. For review 3, 33 studies met the inclusion criteria. Key findings included tensions regarding the preferred format of interventions, particularly how structured interventions were and the extent to which they are tailored to the child with ADHD. There were mixed views about the impact of interventions, although it was clear that interventions both influence and are influenced by the relationships held by children with ADHD and participants' attitudes towards school and ADHD. For review 4, 34 studies met the inclusion criteria. Key findings included the importance of causal attributions that teachers, parents and pupils made about ADHD symptoms, the decisions teachers made about treatment, the self-perceptions pupils developed about themselves, the role of the classroom environment and stigma in aggravating ADHD symptoms, and the significant barrier to treatment posed by the common presence of conflict in relationships between pupils-teachers, parents-teachers and pupils-peers in relation to ADHD. An overarching synthesis of the four reviews highlighted the importance of the context affecting interventions. It suggested that ADHD psychoeducation and relationship-building skills are potential implications for interventions. LIMITATIONS: The breadth of both interventions and outcomes in the reviewed studies presented a challenge for categorisation, analysis and interpretation in reviews 1-3. Across reviews, relatively few studies were conducted in the UK, limiting the applicability of findings to UK education. In reviews 1 and 2, the poor methodological quality of some included studies was identified as a barrier to establishing effectiveness or comparing attitudes. In review 3 the descriptive analysis used by the majority of studies constrained theorising during synthesis. Studies in review 4 lacked detail regarding important issues like gender, pupil maturity and school level. CONCLUSION: Findings suggest some beneficial effects of non-pharmacological interventions for ADHD used in school settings, but substantial heterogeneity in effect sizes was seen across studies. The qualitative reviews demonstrate the importance of the context in which interventions are used. Future work should consider more rigorous evaluation of interventions, as well as focus on what works, for whom and in which contexts. Gaps in current research present opportunities for the development and testing of standardised tools to describe interventions, agreement on gold-standard outcome measures assessing ADHD behaviour and testing a range of potential moderators alongside intervention trials. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001716. FUNDING: The National Institute for Health Research Health Technology Assessment programme.