Intravenous secretin for autism spectrum disorders (ASD).

BACKGROUND: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence. OBJECTIVES: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005. SEARCH METHODS: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. AUTHORS' CONCLUSIONS: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD).

BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of co-morbidity associated with ASD such as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To determine if treatment with an SSRI: 1. improves the core features of autism (social interaction, communication and behavioural problems); 2. improves other non-core aspects of behaviour or function such as self-injurious behaviour; 3. improves the quality of life of children and their carers; 4. has short and long term effects on outcome; 5. causes harms. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE ( December 2009), EMBASE (December 2009), CINAHL (December 2009), PsycINFO (December 2009) and ERIC (December 2009), without language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in participants with autism spectrum disorders. Trials must have included at least one standardised outcome measure. DATA COLLECTION AND ANALYSIS: Two authors independently selected and appraised studies for inclusion and risk of bias. All data were continuous. Meta-analysis, where possible, used a random-effects model. MAIN RESULTS: Seven RCTs with a total of 271 participants were included. Four SSRIs were evaluated: fluoxetine (two studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (one study). Five studies included only children and two studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence of participants. Seventeen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis. One large, high quality study in children showed no evidence of positive effect of citalopram. Two small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression and another in anxiety. AUTHORS' CONCLUSIONS: There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

Iron supplementation for breath-holding attacks in children.

BACKGROUND: Breath-holding attacks are common during childhood. Iron supplementation has been claimed to reduce the frequency or severity, or both, of breath-holding attacks in children. OBJECTIVES: To assess the effect of iron supplementation on the frequency and severity of breath-holding attacks in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL and the metaRegister of Controlled Trials (up to April 2009). We scanned references of included trials. Pharmaceutical companies manufacturing oral iron supplements and some trial authors were contacted for any unpublished data or trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing iron supplementation with placebo or no therapy in children < 18 years with recurrent (more than three) breath-holding episodes. These were reported by an observer. DATA COLLECTION AND ANALYSIS: The primary outcome was reduction in the frequency (number over time) or severity (leading to cessation of loss of consciousness or convulsive movements), or both, of breath-holding attacks. Two authors (AZ and NO) independently selected studies and extracted data. Study authors were contacted for missing data, where necessary. Risk of bias was assessed using domain-based evaluation. In the presence of low heterogeneity, a fixed-effect meta-analysis was performed with pooled results presented as odds ratios (OR) and 95% confidence intervals (CIs). MAIN RESULTS: Two trials (87 children) fulfilled the inclusion criteria. In these trials, iron supplementation significantly reduced the frequency of breath-holding attacks in children (OR 76.48; 95% CI 15.65 to 373.72; P < 0.00001). A meta-analysis that solely examined iron supplementation causing complete resolution of breath-holding attacks maintained this significance (OR 53.43; 95% CI 6.57 to 434.57; P = 0.0002). AUTHORS' CONCLUSIONS: Iron supplementation (at 5 mg/kg/day of elemental iron for 16 weeks) appears to be useful in reducing the frequency and severity of breath-holding attacks. Supplementation is of particular benefit in children with iron deficiency anaemia, responses correlating with the improvements in haemoglobin values. Iron may still be of assistance in children who are not anaemic or who have low, normal haemoglobin levels. Further high-quality randomised control trials of iron supplementation to treat breath-holding attacks in children are required.

Interventions for increasing ankle range of motion in patients with neuromuscular disease.

BACKGROUND: Reduced ankle dorsiflexion range of motion, or ankle equinus, is a common and disabling problem for patients with neuromuscular disease. Clinicians devote considerable time and resources implementing interventions to correct this problem although few of these interventions have been subject to rigorous empirical investigation. OBJECTIVES: To assess the effect of interventions to reduce or resolve ankle equinus in people with neuromuscular disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Specialized Register (August 2009), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2009), MEDLINE (1966 to August 2009), EMBASE (1980 to August 2009), CINAHL 1982 to August 2009), AMED (1985 to August 2009) and The Physiotherapy Evidence Database (PEDro) (1929 to August 2009). We searched the reference lists of identified articles and also contacted known experts in the field to identify additional or unpublished data. SELECTION CRITERIA: Randomised controlled trials evaluating interventions for increasing ankle dorsiflexion range of motion in neuromuscular disease. Outcomes included ankle dorsiflexion range of motion, functional improvement, foot alignment, foot and ankle muscle strength, health-related quality of life, satisfaction with the intervention and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, assessed trial quality and extracted data. MAIN RESULTS: Four studies involving 149 participants met inclusion criteria for this review. Two studies assessed the effect of night splinting in a total of 26 children and adults with Charcot-Marie-Tooth disease type 1A. There were no statistically or clinically significant differences between wearing a night splint and not wearing a night splint. One study assessed the efficacy of prednisone treatment in 103 boys with Duchenne muscular dystrophy. While a daily dose of prednisone at 0.75 mg/kg/day resulted in significant improvements in some strength and function parameters compared with placebo, there was no significant difference in ankle range of motion between groups. Increasing the prednisone dose to 1.5 mg/kg/day had no significant effect on ankle range of motion. One study evaluated early surgery in 20 young boys with Duchenne muscular dystrophy. Surgery resulted in increased ankle dorsiflexion range at 12 months but functional outcomes favoured the control group. By 24 months, many boys in the surgical group experienced a relapse of achilles tendon contractures. AUTHORS' CONCLUSIONS: There is no evidence of significant benefit from any intervention for increasing ankle range of motion in Charcot-Marie-Tooth disease type 1A or Duchenne muscular dystrophy. Further research is required.