Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD).

BACKGROUND: Pharmacological interventions are frequently used for people with autism spectrum disorder (ASD) to manage behaviours of concern, including irritability, aggression, and self-injury. Some pharmacological interventions might help treat some behaviours of concern, but can also have adverse effects (AEs). OBJECTIVES: To assess the effectiveness and AEs of pharmacological interventions for managing the behaviours of irritability, aggression, and self-injury in ASD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 11 other databases and two trials registers up to June 2022. We also searched reference lists of relevant studies, and contacted study authors, experts and pharmaceutical companies. SELECTION CRITERIA: We included randomised controlled trials of participants of any age with a clinical diagnosis of ASD, that compared any pharmacological intervention to an alternative drug, standard care, placebo, or wait-list control. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were behaviours of concern in ASD, (irritability, aggression and self-injury); and AEs. Secondary outcomes were quality of life, and tolerability and acceptability. Two review authors independently assessed each study for risk of bias, and used GRADE to judge the certainty of the evidence for each outcome. MAIN RESULTS: We included 131 studies involving 7014 participants in this review. We identified 26 studies as awaiting classification and 25 as ongoing. Most studies involved children (53 studies involved only children under 13 years), children and adolescents (37 studies), adolescents only (2 studies) children and adults (16 studies), or adults only (23 studies). All included studies compared a pharmacological intervention to a placebo or to another pharmacological intervention. Atypical antipsychotics versus placebo At short-term follow-up (up to 6 months), atypical antipsychotics probably reduce irritability compared to placebo (standardised mean difference (SMD) -0.90, 95% confidence interval (CI) -1.25 to -0.55, 12 studies, 973 participants; moderate-certainty evidence), which may indicate a large effect. However, there was no clear evidence of a difference in aggression between groups (SMD -0.44, 95% CI -0.89 to 0.01; 1 study, 77 participants; very low-certainty evidence). Atypical antipsychotics may also reduce self-injury (SMD -1.43, 95% CI -2.24 to -0.61; 1 study, 30 participants; low-certainty evidence), possibly indicating a large effect. There may be higher rates of neurological AEs (dizziness, fatigue, sedation, somnolence, and tremor) in the intervention group (low-certainty evidence), but there was no clear evidence of an effect on other neurological AEs. Increased appetite may be higher in the intervention group (low-certainty evidence), but we found no clear evidence of an effect on other metabolic AEs. There was no clear evidence of differences between groups in musculoskeletal or psychological AEs. Neurohormones versus placebo At short-term follow-up, neurohormones may have minimal to no clear effect on irritability when compared to placebo (SMD -0.18, 95% CI -0.37 to -0.00; 8 studies; 466 participants; very low-certainty evidence), although the evidence is very uncertain. No data were reported for aggression or self -injury. Neurohormones may reduce the risk of headaches slightly in the intervention group, although the evidence is very uncertain. There was no clear evidence of an effect of neurohormones on any other neurological AEs, nor on any psychological, metabolic, or musculoskeletal AEs (low- and very low-certainty evidence). Attention-deficit hyperactivity disorder (ADHD)-related medications versus placebo At short-term follow-up, ADHD-related medications may reduce irritability slightly (SMD -0.20, 95% CI -0.40 to -0.01; 10 studies, 400 participants; low-certainty evidence), which may indicate a small effect. However, there was no clear evidence that ADHD-related medications have an effect on self-injury (SMD -0.62, 95% CI -1.63 to 0.39; 1 study, 16 participants; very low-certainty evidence). No data were reported for aggression. Rates of neurological AEs (drowsiness, emotional AEs, fatigue, headache, insomnia, and irritability), metabolic AEs (decreased appetite) and psychological AEs (depression) may be higher in the intervention group, although the evidence is very uncertain (very low-certainty evidence). There was no evidence of a difference between groups for any other metabolic, neurological, or psychological AEs (very low-certainty evidence). No data were reported for musculoskeletal AEs. Antidepressants versus placebo At short-term follow-up, there was no clear evidence that antidepressants have an effect on irritability (SMD -0.06, 95% CI -0.30 to 0.18; 3 studies, 267 participants; low-certainty evidence). No data for aggression or self-injury were reported or could be included in the analysis. Rates of metabolic AEs (decreased energy) may be higher in participants receiving antidepressants (very low-certainty evidence), although no other metabolic AEs showed clear evidence of a difference. Rates of neurological AEs (decreased attention) and psychological AEs (impulsive behaviour and stereotypy) may also be higher in the intervention group (very low-certainty evidence) although the evidence is very uncertain. There was no clear evidence of any difference in the other metabolic, neurological, or psychological AEs (very low-certainty evidence), nor between groups in musculoskeletal AEs (very low-certainty evidence). Risk of bias We rated most of the studies across the four comparisons at unclear overall risk of bias due to having multiple domains rated as unclear, very few rated as low across all domains, and most having at least one domain rated as high risk of bias. AUTHORS' CONCLUSIONS: Evidence suggests that atypical antipsychotics probably reduce irritability, ADHD-related medications may reduce irritability slightly, and neurohormones may have little to no effect on irritability in the short term in people with ASD. There was some evidence that atypical antipsychotics may reduce self-injury in the short term, although the evidence is uncertain. There was no clear evidence that antidepressants had an effect on irritability. There was also little to no difference in aggression between atypical antipsychotics and placebo, or self-injury between ADHD-related medications and placebo. However, there was some evidence that atypical antipsychotics may result in a large reduction in self-injury, although the evidence is uncertain. No data were reported (or could be used) for self-injury or aggression for neurohormones versus placebo. Studies reported a wide range of potential AEs. Atypical antipsychotics and ADHD-related medications in particular were associated with an increased risk of metabolic and neurological AEs, although the evidence is uncertain for atypical antipsychotics and very uncertain for ADHD-related medications. The other drug classes had minimal or no associated AEs.

Cost-effectiveness of specialist eating disorders services for children and adolescents with anorexia nervosa: a national surveillance study.

BACKGROUND: Evidence suggests specialist eating disorders services for children and adolescents with anorexia nervosa have the potential to improve outcomes and reduce costs through reduced hospital admissions. This study aimed to evaluate the cost-effectiveness of assessment and diagnosis in community-based specialist child and adolescent mental health services (CAMHS) compared to generic CAMHS for children and adolescents with anorexia nervosa. METHOD: Observational, surveillance study of children and adolescents aged 8 to 17, in contact with community-based CAMHS in the UK or Republic of Ireland for a first episode of anorexia nervosa. Data were reported by clinicians at baseline, 6 and 12-months follow-up. Outcomes included the Children's Global Assessment Scale (CGAS) and percentage of median expected body mass for age and sex (%mBMI). Service use data included paediatric and psychiatric inpatient admissions, outpatient and day-patient attendances. A joint distribution of incremental mean costs and effects for each group was generated using bootstrapping to explore the probability that each service is the optimal choice, subject to a range of values a decision-maker might be willing to pay for outcome improvements. Uncertainty was explored using cost-effectiveness acceptability curves. RESULTS: Two hundred ninety-eight children and adolescents met inclusion criteria. At 12-month follow-up, there were no significant differences in total costs or outcomes between specialist eating disorders services and generic CAMHS. However, adjustment for pre-specified baseline covariates resulted in observed differences favouring specialist services, due to significantly poorer clinical status of the specialist group at baseline. Cost-effectiveness analysis using CGAS suggests that the probability of assessment in a specialist service being cost-effective compared to generic CAMHS ranges from 90 to 50%, dependent on willingness to pay for improvements in outcome. CONCLUSIONS: Assessment in a specialist eating disorders service for children and adolescents with anorexia nervosa may have a higher probability of being cost-effective than assessment in generic CAMHS. TRIAL REGISTRATION: ISRCTN12676087 . Date of registration 07/01/2014.

Specialist eating disorders services may improve outcomes and reduce hospitalisations for children and adolescents with anorexia nervosa. Reductions in hospitalisation could save money for the NHS and are better for young people because hospitalisation disrupts their home life, social life and education. This study evaluated outcomes and costs of specialist eating disorders services compared to general child and adolescent mental health services (CAMHS) for children and adolescents with anorexia nervosa.Children and adolescents were identified by contacting child and adolescent psychiatrists in the UK and Ireland and asking them to report any new cases of anorexia nervosa. These psychiatrists identified 298 young people aged 8 to 17 with an anorexia nervosa diagnosis for the first time. The psychiatrists provided information on the health services these young people used and how they were doing when they were first diagnosed and 6 months and 1 year later.Children and adolescents in specialist services were more severely ill than those in CAMHS when they were first diagnosed. Despite this, care for the young people in specialist services cost about the same as for those diagnosed in CAMHS, and their outcomes after 1 year were similar. This work showed that specialist services may be better value for money than CAMHS.

Cognitive-behavioural therapy (CBT) interventions for young people aged 10 to 18 with harmful sexual behaviour.

BACKGROUND: Around 1 in 1000 adolescents aged 12 to 17 years old display problematic or harmful sexual behaviour (HSB). Examples include behaviours occurring more frequently than would be considered developmentally appropriate; accompanied by coercion; involving children of different ages or stages of development; or associated with emotional distress. Some, but not all, young people engaging in HSB come to the attention of authorities for investigation, prosecution or treatment. Depending on policy context, young people with HSB are those whose behaviour has resulted in a formal reprimand or warning, conviction for a sexual offence, or civil measures. Cognitive-behavioural therapy (CBT) interventions are based on the idea that by changing the way a person thinks, and helping them to develop new coping skills, it is possible to change behaviour. OBJECTIVES: To evaluate the effects of CBT for young people aged 10 to 18 years who have exhibited HSB. SEARCH METHODS: In June 2019, we searched CENTRAL, MEDLINE, Embase, 12 other databases and three trials registers. We also examined relevant websites, checked reference lists and contacted authors of relevant articles. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) using parallel groups. We evaluated CBT treatments compared with no treatment, waiting list or standard care, irrespective of mode of delivery or setting, given to young people aged 10 to 18 years, who had been convicted of a sexual offence or who exhibited HSB. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We found four eligible RCTs (115 participants). Participants in two studies were adolescent males aged 12 to 18 years old. In two studies participants were males simply described as "adolescents." Three studies took place in the USA and one in South Africa. The four studies were of short duration: one lasted two months; two lasted three months; and one lasted six months. No information was available on funding sources. Two studies compared group-based CBT respectively to no treatment (18 participants) or treatment as usual (21 participants). The third compared CBT with sexual education (16 participants). The fourth compared CBT (19 participants) with mode-deactivation therapy (21 participants) and social skills training (20 participants). Three interventions delivered treatment in a residential setting by someone working there, and one in a community setting by licensed therapist undertaking a PhD. CBT compared with no treatment or treatment as usual Primary outcomes No study in this comparison reported the impact of CBT on any measure of primary outcomes (recidivism, and adverse events such as self-harm or suicidal behaviour). Secondary outcomes There was little to no difference between CBT and treatment as usual on cognitive distortions in general (mean difference (MD) 1.56, 95% confidence interval (CI) -11.54 to 14.66, 1 study, 18 participants; very low-certainty evidence), assessed with Abel and Becker Cognition Scale (higher scores indicate more problematic distortions); and specific cognitive distortions about rape (MD 8.75, 95% CI 2.83 to 14.67, 1 study, 21 participants; very low-certainty evidence), measured with the Bumby Cardsort Rape Scale (higher scores indicate more justifications, minimisations, rationalisations and excuses for HSB). One study (18 participants) reported very low-certainty evidence that CBT may result in greater improvements in victim empathy (MD 5.56, 95% CI 0.94 to 10.18), measured with the Attitudes Towards Women Scale, compared with no treatment. One additional study also measured this, but provided no usable data. CBT compared with alternative interventions Primary outcomes One study (59 participants) found little to no difference between CBT and alternative treatments on post-treatment sexual aggression scores (MD 0.09, 95% CI -0.18 to 0.37, very low-certainty evidence), assessed using Daily Behaviour Reports and Behaviour Incidence Report Forms. No study in this comparison reported the impact of CBT on any measure of our remaining primary outcomes. Secondary outcomes One study (16 participants) provided very low-certainty evidence that, compared to sexual education, mean cognitive distortions pertaining to justification or taking responsibility for actions (MD 3.27, 95% CI -4.77 to -1.77) and apprehension confidence (MD 2.47 95% CI -3.85 to -1.09) may be lower in the CBT group. The same study indicated that mean cognitive distortions pertaining to social-sexual desirability may be lower in the CBT group, and there may be little to no difference between the groups for cognitive distortions pertaining to inappropriate sexual fantasies measured with the Multiphasic Sex Inventory. AUTHORS' CONCLUSIONS: It is uncertain whether CBT reduces HSB in male adolescents compared to other treatments. All studies had insufficient detail in what they reported to allow for full assessment of risk of bias. 'Risk of bias' judgements were predominantly rated as unclear or high. Sample sizes were very small, and the imprecision of results was significant. There is very low-certainty evidence that group-based CBT may improve victim empathy when compared to no treatment, and may improve cognitive distortions when compared to sexual education, but not treatment as usual. Further research is likely to change the estimate. More robust evaluations of both individual and group-based CBT are required, particularly outside North America, and which look at the effects of CBT on diverse participants.

Video feedback for parental sensitivity and attachment security in children under five years.

BACKGROUND: Children who are securely attached to at least one parent are able to be comforted by that parent when they are distressed and explore the world confidently by using that parent as a 'secure base'. Research suggests that a secure attachment enables children to function better across all aspects of their development. Promoting secure attachment, therefore, is a goal of many early interventions. Attachment is mediated through parental sensitivity to signals of distress from the child. One means of improving parental sensitivity is through video feedback, which involves showing a parent brief moments of their interaction with their child, to strengthen their sensitivity and responsiveness to their child's signals. OBJECTIVES: To assess the effects of video feedback on parental sensitivity and attachment security in children aged under five years who are at risk for poor attachment outcomes. SEARCH METHODS: In November 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, nine other databases and two trials registers. We also handsearched the reference lists of included studies, relevant systematic reviews, and several relevant websites SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that assessed the effects of video feedback versus no treatment, inactive alternative intervention, or treatment as usual for parental sensitivity, parental reflective functioning, attachment security and adverse effects in children aged from birth to four years 11 months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes 22 studies from seven countries in Europe and two countries in North America, with a total of 1889 randomised parent-child dyads or family units. Interventions targeted parents of children aged under five years, experiencing a wide range of difficulties (such as deafness or prematurity), or facing challenges that put them at risk of attachment issues (for example, parental depression). Nearly all studies reported some form of external funding, from a charitable organisation (n = 7) or public body, or both (n = 18). We considered most studies as being at low or unclear risk of bias across the majority of domains, with the exception of blinding of participants and personnel, where we assessed all studies as being at high risk of performance bias. For outcomes where self-report measures were used, such as parental stress and anxiety, we rated all studies at high risk of bias for blinding of outcome assessors. Parental sensitivity. A meta-analysis of 20 studies (1757 parent-child dyads) reported evidence of that video feedback improved parental sensitivity compared with a control or no intervention from postintervention to six months' follow-up (standardised mean difference (SMD) 0.34, 95% confidence interval (CI) 0.20 to 0.49, moderate-certainty evidence). The size of the observed impact compares favourably to other, similar interventions. Parental reflective functioning. No studies reported this outcome. Attachment security. A meta-analysis of two studies (166 parent-child dyads) indicated that video feedback increased the odds of being securely attached, measured using the Strange Situation Procedure, at postintervention (odds ratio 3.04, 95% CI 1.39 to 6.67, very low-certainty evidence). A second meta-analysis of two studies (131 parent-child dyads) that assessed attachment security using a different measure (Attachment Q-sort) found no effect of video feedback compared with the comparator groups (SMD 0.02, 95% CI -0.33 to 0.38, very low-certainty evidence). Adverse events. Eight studies (537 parent-child dyads) contributed data at postintervention or short-term follow-up to a meta-analysis of parental stress, and two studies (311 parent-child dyads) contributed short-term follow-up data to a meta-analysis of parental anxiety. There was no difference between intervention and comparator groups for either outcome. For parental stress the SMD between video feedback and control was -0.09 (95% CI -0.26 to 0.09, low-certainty evidence), while for parental anxiety the SMD was -0.28 (95% CI -0.87 to 0.31, very low-certainty evidence). Child behaviour. A meta-analysis of two studies (119 parent-child dyads) at long-term follow-up found no evidence of the effectiveness of video feedback on child behaviour (SMD 0.04, 95% CI -0.33 to 0.42, very low-certainty evidence). A moderator analysis found no evidence of an effect for the three prespecified variables (intervention type, number of feedback sessions and participating carer) when jointly tested. However, parent gender (both parents versus only mothers or only fathers) potentially has a statistically significant negative moderation effect, though only at α (alpha) = 0.1 AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that video feedback may improve sensitivity in parents of children who are at risk for poor attachment outcomes due to a range of difficulties. There is currently only little, very low-certainty evidence regarding the impact of video feedback on attachment security, compared with control: results differed based on the type of measure used, and follow-up was limited in duration. There is no evidence that video feedback has an impact on parental stress or anxiety (low- and very low-certainty evidence, respectively). Further evidence is needed regarding the longer-term impact of video feedback on attachment and more distal outcomes such as children's behaviour (very low-certainty evidence). Further research is needed on the impact of video-feedback on paternal sensitivity and parental reflective functioning, as no study measured these outcomes. This review is limited by the fact that the majority of included parents were mothers.

Incidence of anorexia nervosa in young people in the UK and Ireland: a national surveillance study.

OBJECTIVES: This study aimed to estimate the incidence of DSM5 anorexia nervosa in young people in contact with child and adolescent mental health services in the UK and Ireland. DESIGN: Observational, surveillance study, using the Child and Adolescent Psychiatry Surveillance System, involving monthly reporting by child and adolescent psychiatrists between 1st February 2015 and 30th September 2015. SETTING: The study was based in the UK and Ireland. PARTICIPANTS: Clinician-reported data on young people aged 8-17 in contact with child and adolescent mental health services for a first episode of anorexia nervosa. MAIN OUTCOME MEASURES: Annual incidence rates (IRs) estimated as confirmed new cases per 100 000 population at risk. RESULTS: 305 incident cases of anorexia nervosa were reported over the 8-month surveillance period and assessed as eligible for inclusion. The majority were young women (91%), from England (70%) and of white ethnicity (92%). Mean age was 14.6 years (±1.66) and mean percentage of median expected body mass index for age and sex was 83.23% (±10.99%). The overall IR, adjusted for missing data, was estimated to be 13.68 per 100 000 population (95% CI 12.88 to 14.52), with rates of 25.66 (95% CI 24.09 to 27.30) for young women and 2.28 (95% CI 1.84 to 2.79) for young men. Incidence increased steadily with age, peaking at 15 (57.77, 95% CI 50.41 to 65.90) for young women and 16 (5.14, 95% CI 3.20 to 7.83) for young men. Comparison with earlier estimates suggests IRs for children aged 12 and under have increased over the last 10 years. CONCLUSION: These results provide new estimates of the incidence of anorexia nervosa in young people. Service providers and commissioners should consider evidence to suggest an increase in incidence in younger children. TRIAL REGISTRATION NUMBER: ISRCTN12676087.

Diagnostic tests for autism spectrum disorder (ASD) in preschool children.

BACKGROUND: Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive behaviours, or both. Diagnosis is made according to existing classification systems. In recent years, especially following publication of the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5; APA 2013), children are given the diagnosis of ASD, rather than subclassifications of the spectrum such as autistic disorder, Asperger syndrome, or pervasive developmental disorder - not otherwise specified. Tests to diagnose ASD have been developed using parent or carer interview, child observation, or a combination of both. OBJECTIVES: Primary objectives1. To identify which diagnostic tools, including updated versions, most accurately diagnose ASD in preschool children when compared with multi-disciplinary team clinical judgement.2. To identify how the best of the interview tools compare with CARS, then how CARS compares with ADOS.a. Which ASD diagnostic tool - among ADOS, ADI-R, CARS, DISCO, GARS, and 3di - has the best diagnostic test accuracy?b. Is the diagnostic test accuracy of any one test sufficient for that test to be suitable as a sole assessment tool for preschool children?c. Is there any combination of tests that, if offered in sequence, would provide suitable diagnostic test accuracy and enhance test efficiency?d. If data are available, does the combination of an interview tool with a structured observation test have better diagnostic test accuracy (i.e. fewer false-positives and fewer false-negatives) than either test alone?As only one interview tool was identified, we modified the first three aims to a single aim (Differences between protocol and review): This Review evaluated diagnostic tests in terms of sensitivity and specificity. Specificity is the most important factor for diagnosis; however, both sensitivity and specificity are of interest in this Review because there is an inherent trade-off between these two factors.Secondary objectives1. To determine whether any diagnostic test has greater diagnostic test accuracy for age-specific subgroups within the preschool age range. SEARCH METHODS: In July 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and the reference lists of all included publications. SELECTION CRITERIA: Publications had to: 1. report diagnostic test accuracy for any of the following six included diagnostic tools: Autism Diagnostic Interview - Revised (ADI-R), Gilliam Autism Rating Scale (GARS), Diagnostic Interview for Social and Communication Disorder (DISCO), Developmental, Dimensional, and Diagnostic Interview (3di), Autism Diagnostic Observation Schedule - Generic (ADOS), and Childhood Autism Rating Scale (CARS); 2. include children of preschool age (under six years of age) suspected of having an ASD; and 3. have a multi-disciplinary assessment, or similar, as the reference standard.Eligible studies included cohort, cross-sectional, randomised test accuracy, and case-control studies. The target condition was ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all studies for inclusion and extracted data using standardised forms. A third review author settled disagreements. We assessed methodological quality using the QUADAS-2 instrument (Quality Assessment of Studies of Diagnostic Accuracy - Revised). We conducted separate univariate random-effects logistical regressions for sensitivity and specificity for CARS and ADI-R. We conducted meta-analyses of pairs of sensitivity and specificity using bivariate random-effects methods for ADOS. MAIN RESULTS: In this Review, we included 21 sets of analyses reporting different tools or cohorts of children from 13 publications, many with high risk of bias or potential conflicts of interest or a combination of both. Overall, the prevalence of ASD for children in the included analyses was 74%.For versions and modules of ADOS, there were 12 analyses with 1625 children. Sensitivity of ADOS ranged from 0.76 to 0.98, and specificity ranged from 0.20 to 1.00. The summary sensitivity was 0.94 (95% confidence interval (CI) 0.89 to 0.97), and the summary specificity was 0.80 (95% CI 0.68 to 0.88).For CARS, there were four analyses with 641 children. Sensitivity of CARS ranged from 0.66 to 0.89, and specificity ranged from 0.21 to 1.00. The summary sensitivity for CARS was 0.80 (95% CI 0.61 to 0.91), and the summary specificity was 0.88 (95% CI 0.64 to 0.96).For ADI-R, there were five analyses with 634 children. Sensitivity for ADI-R ranged from 0.19 to 0.75, and specificity ranged from 0.63 to 1.00. The summary sensitivity for the ADI-R was 0.52 (95% CI 0.32 to 0.71), and the summary specificity was 0.84 (95% CI 0.61 to 0.95).Studies that compared tests were few and too small to allow clear conclusions.In two studies that included analyses for both ADI-R and ADOS, tests scored similarly for sensitivity, but ADOS scored higher for specificity. In two studies that included analyses for ADI-R, ADOS, and CARS, ADOS had the highest sensitivity and CARS the highest specificity.In one study that explored individual and additive sensitivity and specificity of ADOS and ADI-R, combining the two tests did not increase the sensitivity nor the specificity of ADOS used alone.Performance for all tests was lower when we excluded studies at high risk of bias. AUTHORS' CONCLUSIONS: We observed substantial variation in sensitivity and specificity of all tests, which was likely attributable to methodological differences and variations in the clinical characteristics of populations recruited.When we compared summary statistics for ADOS, CARS, and ADI-R, we found that ADOS was most sensitive. All tools performed similarly for specificity. In lower prevalence populations, the risk of falsely identifying children who do not have ASD would be higher.Now available are new versions of tools that require diagnostic test accuracy assessment, ideally in clinically relevant situations, with methods at low risk of bias and in children of varying abilities.

Parents Suggest Which Indicators of Progress and Outcomes Should be Measured in Young Children with Autism Spectrum Disorder.

Evaluation of interventions for children with autism spectrum disorder (ASD) is hampered by the multitude of outcomes measured and tools used. Measurement in research with young children tends to focus on core impairments in ASD. We conducted a systematic review of qualitative studies of what matters to parents. Parent advisory groups completed structured activities to explore their perceptions of the relative importance of a wide range of outcome constructs. Their highest ranked outcomes impacted directly on everyday life and functioning (anxiety, distress, hypersensitivity, sleep problems, happiness, relationships with brothers and sisters, and parent stress). Collaboration between professionals, researchers and parents/carers is required to determine an agreed core set of outcomes to use across evaluation research.

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Systematic Review of the Measurement Properties of Tools Used to Measure Behaviour Problems in Young Children with Autism.

BACKGROUND: Behaviour problems are common in young children with autism spectrum disorder (ASD). There are many different tools used to measure behavior problems but little is known about their validity for the population. OBJECTIVES: To evaluate the measurement properties of behaviour problems tools used in evaluation of intervention or observational research studies with children with ASD up to the age of six years. METHODS: Behaviour measurement tools were identified as part of a larger, two stage, systematic review. First, sixteen major electronic databases, as well as grey literature and research registers were searched, and tools used listed and categorized. Second, using methodological filters, we searched for articles examining the measurement properties of the tools in use with young children with ASD in ERIC, MEDLINE, EMBASE, CINAHL, and PsycINFO. The quality of these papers was then evaluated using the COSMIN checklist. RESULTS: We identified twelve tools which had been used to measure behaviour problems in young children with ASD, and fifteen studies which investigated the measurement properties of six of these tools. There was no evidence available for the remaining six tools. Two questionnaires were found to be the most robust in their measurement properties, the Child Behavior Checklist and the Home Situations Questionnaire-Pervasive Developmental Disorders version. CONCLUSIONS: We found patchy evidence on reliability and validity, for only a few of the tools used to measure behaviour problems in young children with ASD. More systematic research is required on measurement properties of tools for use in this population, in particular to establish responsiveness to change which is essential in measurement of outcomes of intervention. PROSPERO REGISTRATION NUMBER: CRD42012002223.

Pharmacological interventions for cognitive decline in people with Down syndrome.

BACKGROUND: People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear. OBJECTIVES: To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome. SEARCH METHODS: In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary. MAIN RESULTS: Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures. AUTHORS' CONCLUSIONS: Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.

Systematic review of tools to measure outcomes for young children with autism spectrum disorder.

BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact. OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents. METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers. RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents). CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research. FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Household interventions for preventing domestic lead exposure in children.

BACKGROUND: Lead poisoning is associated with physical, cognitive and neurobehavioural impairment in children and trials have tested many household interventions to prevent lead exposure. This is an update of the original review by the same authors first published in 2008. OBJECTIVES: To determine the effectiveness of household interventions in preventing or reducing lead exposure in children as measured by reductions in blood lead levels and/or improvements in cognitive development. SEARCH METHODS: We identified trials through electronic searches of CENTRAL (2012, Issue 1), MEDLINE (1948 to January Week 1 2012), EMBASE (1980 to Week 2 2012), CINAHL (1937 to January 2012), PsycINFO (1887 to January Week 2 2012), ERIC (1966 to January 2012), Sociological Abstracts (1952 to January 2012), Science Citation Index (1970 to 20 January 2012), ZETOC (20 January 2012), LILACS (20 January 2012), Dissertation Abstracts (late 1960s to January 2012), ClinicalTrials.gov (19 January 2012), Current Controlled Trials (19 January 2012), Australian New Zealand Clinical Trials Registry (19 January 2012) and the National Research Register Archive. We also contacted experts to find unpublished studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of household educational or environmental interventions to prevent lead exposure in children where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. MAIN RESULTS: We included 14 studies (involving 2656 children). All studies reported blood lead level outcomes and none reported on cognitive or neurobehavioural outcomes. We put studies into subgroups according to their intervention type. We performed meta-analysis of both continuous and dichotomous data for subgroups where appropriate. Educational interventions were not effective in reducing blood lead levels (continuous: mean difference (MD) 0.02, 95% confidence interval (CI) -0.09 to 0.12, I(2) = 0 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): relative risk (RR) 1.02, 95% CI 0.79 to 1.30, I(2)=0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.60, 95% CI 0.33 to 1.09, I(2) = 0). Meta-analysis for the dust control subgroup also found no evidence of effectiveness (continuous: MD -0.15, 95% CI -0.42 to 0.11, I(2) = 0.9 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): RR 0.93, 95% CI 0.73 to 1.18, I(2) =0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.86, 95% CI 0.35 to 2.07, I(2) = 0.56). When meta-analysis for the dust control subgroup was adjusted for clustering, no statistical significant benefit was incurred. The studies using soil abatement (removal and replacement) and combination intervention groups were not able to be meta-analysed due to substantial differences between studies. AUTHORS' CONCLUSIONS: Based on current knowledge, household educational or dust control interventions are ineffective in reducing blood lead levels in children as a population health measure. There is currently insufficient evidence to draw conclusions about the effectiveness of soil abatement or combination interventions.Further trials are required to establish the most effective intervention for prevention of lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in developing countries and in differing socioeconomic groups in developed countries.

Primary reflex persistence in children with partial hearing.

Persistence of the asymmetrical tonic neck reflex (ATNR) was examined in children with partial hearing (aged 6-12 years). Core literacy skills were also assessed. Three groups of children were selected from three schools with special units for children with partial hearing. All children completed an upright ATNR test protocol and standardized tests of reading and spelling. Children with partial hearing had significant levels of ATNR persistence, and significant reading and spelling difficulties. The findings suggest that persistence of an early sub-cortical reflex system may be associated with some of the motor and cognitive difficulties experienced by children with partial hearing.

Restorative justice conferencing for reducing recidivism in young offenders (aged 7 to 21).

BACKGROUND: Restorative justice is "a process whereby parties with a stake in a specific offence resolve collectively how to deal with the aftermath of the offence and its implications for the future" (Marshall 2003). Despite the increasing use of restorative justice programmes as an alternative to court proceedings, no systematic review has been undertaken of the available evidence on the effectiveness of these programmes with young offenders. Recidivism in young offenders is a particularly worrying problem, as recent surveys have indicated the frequency of re-offences for young offenders has ranged from 40.2% in 2000 to 37.8% in 2007 (Ministry of Justice 2009) OBJECTIVES: To evaluate the effects of restorative justice conferencing programmes for reducing recidivism in young offenders. SEARCH METHODS: We searched the following databases up to May 2012: CENTRAL, 2012 Issue 5, MEDLINE (1978 to current), Bibliography of Nordic Criminology (1999 to current), Index to Theses (1716 to current), PsycINFO (1887 to current), Social Sciences Citation Index (1970 to current), Sociological Abstracts (1952 to current), Social Care Online (1985 to current), Restorative Justice Online (1975 to current), Scopus (1823 to current), Science Direct (1823 to current), LILACS (1982 to current), ERIC (1966 to current), Restorative Justice Online (4 May 2012), WorldCat (9 May 2012), ClinicalTrials.gov (19 May 2012) and ICTRP (19 May 2012). ASSIA, National Criminal Justice Reference Service and Social Services Abstracts were searched up to May 2011. Relevant bibliographies, conference programmes and journals were also searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of restorative justice conferencing versus management as usual, in young offenders. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias of included trials and extracted the data. Where necessary, original investigators were contacted to obtain missing information. MAIN RESULTS: Four trials including a total of 1447 young offenders were included in the review. Results failed to find a significant effect for restorative justice conferencing over normal court procedures for any of the main analyses, including number re-arrested (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.59 to 1.71; P = 0.99), monthly rate of reoffending (standardised mean difference (SMD) -0.06, 95% CI -0.28 to 0.16; P = 0.61), young person's remorse following conference (OR 1.73, 95% CI 0.97 to 3.10; P = 0.06), young person's recognition of wrongdoing following conference (OR 1.97, 95% CI 0.81 to 4.80; P = 0.14), young person's self-perception following conference (OR 0.95, 95% CI 0.55 to 1.63; P = 0.85), young person's satisfaction following conference (OR 0.42, 95% CI 0.04 to 4.07; P = 0.45) and victim's satisfaction following conference (OR 4.05, 95% CI 0.56 to 29.04; P = 0.16). A small number of sensitivity analyses did indicate significant effects, although all are to be interpreted with caution. AUTHORS' CONCLUSIONS: There is currently a lack of high quality evidence regarding the effectiveness of restorative justice conferencing for young offenders. Caution is urged in interpreting the results of this review considering the small number of included studies, subsequent low power and high risk of bias. The effects may potentially be more evident for victims than offenders. The need for further research in this area is highlighted.

Household interventions for preventing domestic lead exposure in children.

BACKGROUND: Lead poisoning is associated with physical, cognitive and neurobehavioural impairment in children and trials have tested many household interventions to prevent lead exposure. This is an update of the original review by the same authors first published in 2008. OBJECTIVES: To determine the effectiveness of household interventions in preventing or reducing lead exposure in children as measured by reductions in blood lead levels and/or improvements in cognitive development. SEARCH METHODS: We identified trials through electronic searches of CENTRAL (The Cochrane Library, 2010, Issue 2), MEDLINE (1948 to April Week 1 2012), EMBASE (1980 to 2012 Week 2), CINAHL (1937 to 20 Jan 2012), PsycINFO (1887 to Dec week 2 2011), ERIC (1966 to 17 Jan 2012), Sociological Abstracts (1952 to 20 January 2012), Science Citation Index (1970 to 20 Jan 2012), ZETOC (20 Jan 2012), LILACS (20 Jan 2012), Dissertation Abstracts (late 1960s to Jan 2012), ClinicalTrials.gov (20 Jan 2012), Current Controlled Trials (Jan 2012), Australian New Zealand Clinical Trials Registry (Jan 2012) and the National Research Register Archive. We also contacted experts to find unpublished studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of household educational or environmental interventions to prevent lead exposure in children where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. MAIN RESULTS: We included 14 studies (involving 2656 children). All studies reported blood lead level outcomes and none reported on cognitive or neurobehavioural outcomes. We put studies into subgroups according to their intervention type. We performed meta-analysis of both continuous and dichotomous data for subgroups where appropriate. Educational interventions were not effective in reducing blood lead levels (continuous: mean difference (MD) 0.02, 95% confidence interval (CI) -0.09 to 0.12, I(2) = 0 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): relative risk (RR) 1.02, 95% CI 0.79 to 1.30, I(2)=0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.60, 95% CI 0.33 to 1.09, I(2) = 0). Meta-analysis for the dust control subgroup also found no evidence of effectiveness (continuous: MD -0.15, 95% CI -0.42 to 0.11, I(2) = 0.9 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): RR 0.93, 95% CI 0.73 to 1.18, I(2) =0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.86, 95% CI 0.35 to 2.07, I(2) = 0.56). When meta-analysis for the dust control subgroup was adjusted for clustering, no statistical significant benefit was incurred. The studies using soil abatement (removal and replacement) and combination intervention groups were not able to be meta-analysed due to substantial differences between studies. AUTHORS' CONCLUSIONS: Based on current knowledge, household educational or dust control interventions are ineffective in reducing blood lead levels in children as a population health measure. There is currently insufficient evidence to draw conclusions about the effectiveness of soil abatement or combination interventions.Further trials are required to establish the most effective intervention for prevention of lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in developing countries and in differing socioeconomic groups in developed countries.

Motor skill deficits in children with partial hearing.

AIM: We examined the effect of partial hearing, including cochlear implantation, on the development of motor skills in children (aged 6-12y). METHOD: Three independent groups of children were selected: a partial hearing group (n=25 [14 males, 11 females]; mean age 8y 8mo, SD 1y 10mo), a nonverbal IQ-matched group (n=27 [15 males, 12 females]; mean age 9y, SD 1y 6mo), and an age-matched group (n=26 [8 males, 18 females]; mean age 8y 8mo, SD 1y 7mo) from three schools with special units for children with partial hearing. All children with partial hearing had a bilateral hearing loss >60 decibels. Motor and balance skills were assessed using the Movement Assessment Battery for Children (MABC) and two protocols from the NeuroCom Balance Master clinical procedures. RESULTS: The mean standardized total MABC score of the children with partial hearing (95% confidence interval [CI] 71.8-88.7) was significantly lower than both the age-matched (95% CI 95.8-111.4; p<0.01) and the IQ-matched (95% CI 87.6-103.0; p=0.03) comparison groups. The children with partial hearing had particular difficulties with balance, most notably during tests of intersensory demand. However, subgroup analyses revealed that the effect of cochlear implantation was clearly dependent on the nature of the task. INTERPRETATION: Children with partial hearing are at high risk of clinical levels of motor deficit, with balance difficulties providing support for conventional vestibular deficit theory. However, the effect of cochlear implantation suggests that other sensory systems may be involved. A broader ecological perspective, which takes into account factors external to the child, may prove a useful framework for future research.