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Journal ArticleDOI

Intravenous secretin for autism spectrum disorders (ASD).

TL;DR: 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.
Abstract: 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 We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies.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.

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Citations
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Patent
12 Oct 2011
TL;DR: A therapeutic agent for the treatment of the symptoms of addiction and the method for preparing the therapeutic agent is disclosed in this paper, where a stable pharmaceutical preparation containing, but not limited to, digestive/pancreatic enzymes.
Abstract: A therapeutic agent for the treatment of the symptoms of addiction and the method for preparing the therapeutic agent is disclosed. The therapeutic agent is a stable pharmaceutical preparation containing, but not limited to, digestive/pancreatic enzymes. The therapeutic agent may be manufactured by a variety of encapsulation technologies. Delivery of the therapeutic agent may be made orally, through injection, by adherence of a medicated patch or other method. Further, a method of using of a biomarker, the presence of chymotrypsin in the gastrointestinal tract to determine the presence of symptoms of addiction, and the likelihood of relapsing into addiction is disclosed.

27 citations

Book ChapterDOI
01 Jan 2011
TL;DR: The authors defined challenging behavior as "culturally abnormal behavior(s) of such intensity, frequency or duration that the physical safety of the person or others is likely to be placed in serious jeopardy, or behavior which is likely, seriously, or severely limit use of, or result in the person being denied access to, ordinary community facilities".
Abstract: By definition, individuals with autism have severe difficulties in reciprocal relationships, verbal and nonverbal communication, unusual repetitive behavior, and restricted interests (American Psychiatric Association, 2000). Furthermore, in about 75–80% of cases, autism is comorbid with intellectual disabilities (National Research Council, 2001). Epidemiological studies indicate that 10–15% of individuals with intellectual disabilities engage in problem behaviors, or what is currently termed “challenging behaviors” (Holden & Gitlesen, 2006; Lowe et al., 2007; Murphy et al., 2005). Challenging behaviors have been defined as “culturally abnormal behavior(s) of such intensity, frequency or duration that the physical safety of the person or others is likely to be placed in serious jeopardy, or behavior which is likely to seriously limit use of, or result in the person being denied access to, ordinary community facilities” (Emerson, 2001, p. 3). Aggression, tantrums, property destruction, disruptive behavior, and self-injury are examples of challenging behavior often displayed by individuals with autism and pervasive developmental disorders.

27 citations

Journal Article
TL;DR: It is important for physicians to know the current evidence which examines the use of CAM treatments in children and adolescents with autism so that they may have conversations with families which are informed and evidence-based.
Abstract: Complementary alternative medicine (CAM) is used to a greater degree in children and adolescents with autism spectrum disorder (ASD), when compared to children and adolescents without this diagnosis. There is limited evidence supporting the use of many of these treatments in ASD, despite their popularity. Current FDA approved medications for ASD target associated behavioral symptoms of the diagnosis, not the core symptoms of social communication deficits and restricted/repetitive behaviors. These medications are also associated with concerning adverse effects. Evidence-based therapies for core symptoms, such as applied behavior analysis (ABA), are sometimes difficult for families to access for various reasons. Families are sometimes hesitant to discuss their interest in CAM with physicians. Physicians report knowledge gaps about CAM and their use in ASD and concerns about potential conflict with parents regarding differing beliefs of CAM's role in the management of ASD. It is important for physicians to know the current evidence which examines the use of CAM treatments in children and adolescents with autism so that they may have conversations with families which are informed and evidence-based.

26 citations

Journal ArticleDOI
TL;DR: The evidence base for targeting specific symptoms and disorders with psychopharmacology in children with autism spectrum disorder is expanding rapidly and offers guidance for practicing clinicians.

26 citations

Patent
26 Jun 2009
TL;DR: A therapeutic composition for the treatment of the symptoms of Williams Syndrome and the method for preparing the therapeutic agents is disclosed in this article, where the therapeutic composition is a stable pharmaceutical composition comprising one or more digestive and/or pancreatic enzymes.
Abstract: A therapeutic composition for the treatment of the symptoms of Williams Syndrome and the method for preparing the therapeutic agents is disclosed. The therapeutic composition is a stable pharmaceutical composition comprising one or more digestive and/or pancreatic enzymes. The therapeutic composition may be manufactured by a variety of encapsulation technologies. Delivery of the therapeutic composition may be made orally, through injection, by adherence of a medicated patch or other method. Further, a method of using fecal chymotrypsin level as a biomarker for the presence of Williams Syndrome, or the likelihood of an individual to develop Williams Syndrome is disclosed.

25 citations

References
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Journal ArticleDOI
13 Sep 1997-BMJ
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

37,989 citations

Journal ArticleDOI
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Abstract: The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.

25,460 citations

Book
23 Sep 2019
TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

21,235 citations

Book
01 Jun 1991

12,618 citations


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