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 We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies.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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TL;DR: Important issues, such as management of associated medical problems, pharmacologic and nonpharmacologic intervention for challenging behaviors or coexisting mental health conditions, and use of complementary and alternative medical treatments, are also addressed.
Abstract: Pediatricians have an important role not only in early recognition and evaluation of autism spectrum disorders but also in chronic management of these disorders. The primary goals of treatment are to maximize the child's ultimate functional independence and quality of life by minimizing the core autism spectrum disorder features, facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families. To assist pediatricians in educating families and guiding them toward empirically supported interventions for their children, this report reviews the educational strategies and associated therapies that are the primary treatments for children with autism spectrum disorders. Optimization of health care is likely to have a positive effect on habilitative progress, functional outcome, and quality of life; therefore, important issues, such as management of associated medical problems, pharmacologic and nonpharmacologic intervention for challenging behaviors or coexisting mental health conditions, and use of complementary and alternative medical treatments, are also addressed.
1,010 citations
TL;DR: Early, sustained intervention and the use of multiple treatment modalities are indicated in patients with an autism spectrum disorder.
Abstract: Autism spectrum disorder is characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills that arise in the first years of life. Although frequently associated with intellectual disability, this condition is distinctive in its course, impact, and treatment. Autism spectrum disorder has a wide range of syndrome expression and its management presents particular challenges for clinicians. Individuals with an autism spectrum disorder can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with this condition necessitate multidisciplinary care, coordination of services, and advocacy for individuals and their families. Early, sustained intervention and the use of multiple treatment modalities are indicated. J. Am. Acad. Child Adolesc. Psychiatry, 2014;53(2):237–257. Key Words: autism, Practice Parameters, guidelines, developmental disorders, pervasive developmental disorders
677 citations
TL;DR: Evidence for the effectiveness of EIBI for some, but not all, preschool children with autism is provided, with some evidence that initial IQ (but not age) was related to progress.
Abstract: Recent reviews highlight limitations in the evidence base for early interventions for children with autism. We conducted a systematic review of controlled studies of early intensive behavioral interventions (EIBI) for young children with autism. Eleven studies met inclusion criteria (including two randomized controlled trials). At group level, EIBI resulted in improved outcomes (primarily measured by IQ) compared to comparison groups. At an individual level, however, there was considerable variability in outcome, with some evidence that initial IQ (but not age) was related to progress. This review provides evidence for the effectiveness of EIBI for some, but not all, preschool children with autism.
495 citations
TL;DR: In this study, 128 meta-analyses from Cochrane reviews, containing data on at least 1 adult and 1 pediatric randomized controlled trial (RCT) with a binary primary efficacy outcome, were reviewed and it was found that in all except 1 case, the 95% confidence intervals could not exclude a relative difference in treatment efficacy between adults and children of >20%.
Abstract: * Abbreviations:
RCT — : randomized controlled trial
SSRI — : selective serotonin reuptake inhibitor
It has long been an axiom in clinical pediatrics that “children are not just little adults.” It has also been recognized that there are many changes from birth through childhood and the adolescent years. However, the full implications of pediatric age groupings for health care and research are still not adequately understood. There is still much to be discovered about children’s biological and psychological development and how these processes affect the effectiveness and efficacy of interventions. Trial design that accounts for age differences and promotes consistency in reporting of age-related data is essential to ensure the validity and clinical usefulness of pediatric trial data.
A recent study highlighted variable treatment efficacy in children versus adults. In this study, 128 meta-analyses from Cochrane reviews, containing data on at least 1 adult and 1 pediatric randomized controlled trial (RCT) with a binary primary efficacy outcome, were reviewed.1 The authors found that in all except 1 case, the 95% confidence intervals could not exclude a relative difference in treatment efficacy between adults and children of >20%; in two-thirds of these cases, the relative difference in observed point estimates was >50%. The study also highlighted the paucity of RCTs in pediatrics; the median number of children per meta-analysis was 2.5 times smaller than the number of adults.
Children and adults seem to have distinctive responses to treatments. For example, administration of phenobarbitones is useful for adults with cerebral malaria and is associated with decreased convulsions. However, in children, this drug is associated with increased 6-month mortality. Similarly, corticosteroids may offer survival benefit for adults with bacterial meningitis but not for children with the same condition. In acute traumatic brain injury, corticosteroids did not decrease mortality in adults, but there was a trend for increased mortality in children.1 In asthma, long-acting β2-agonists decreased …
Address correspondence to Martin Offringa, MD, PhD, Senior Scientist and Program Head, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: martin.offringa{at}sickkids.ca
356 citations
TL;DR: As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.
Abstract: OBJECTIVE: To determine whether children with autism have an increased incidence of gastrointestinal symptoms compared with matched control subjects in a population-based sample. DESIGN/METHODS: In a previous study including all of the residents of Olmsted County, Minnesota, aged RESULTS: Subjects were followed to median ages of 18.2 (case subjects) and 18.7 (control subjects) years. Significant differences between autism case and control subjects were identified in the cumulative incidence of constipation (33.9% vs 17.6%) and feeding issues/food selectivity (24.5% vs 16.1). No significant associations were found between autism case status and overall incidence of gastrointestinal symptoms or any other gastrointestinal symptom category. CONCLUSIONS: As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.
264 citations
References
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TL;DR: The revised CONSORT statement as discussed by the authors is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results, which can be achieved only through complete transparency from authors.
Abstract: To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Comment. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from 4 stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, according to each intervention group, included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
2,955 citations
TL;DR: The Mullen Scales of Early Learning (MSEL) as mentioned in this paper includes five scales that provide information on cognitive and motor ability, including Gross Motor (0-33 months only), Visual Reception, Fine Motor, Expressive Language and Receptive Language.
Abstract: Short Description of Instrument: Description: The Mullen Scales of Early Learning (MSEL) includes five scales that provide information on cognitive and motor ability. The five scales include: Gross Motor (0–33 months only), Visual Reception, Fine Motor, Expressive Language and Receptive Language. In addition to assessing a child’s strength and weaknesses, this measure is used to assess school readiness. Included in the questionnaire are three different forms depending on the age of the child; 15 minute test for a 1-year old, 25– 35 minute test for 3 year olds and 40–60 minutes for 5 year olds. The report generated from this measure includes a list of tasks that parents can help their child learn at home (based on age).
2,320 citations
TL;DR: In 1966, when an outpatient treatment program for autistic children and their families was initiated, there were two major sets of guidelines for diagnosing the children who were referred to the program, and the most promising at tempt to translate the Kanner definition into an empirical rating scale was the Rimland Checklist.
Abstract: In 1966, when we initiated an outpatient treatment program for autistic children and their families (Schopler & Reichler, 1971), there were two major sets of guidelines for diagnosing the children who were referred to our program. The first was Kanner ' s (1943) original definition of autism. At the start of our program the most promising at tempt to translate the Kanner definition into an empirical rating scale was the Rimland Checklist (1964), later revised into a second form (Rimland, 1971). This checklist was completed for all children evaluated in our program. From the very beginning, however, we had the clinical impression that very few of our children were autistic according to Kanner ' s criteria. The Creak (1964) criteria served as a second system of classification. Like Kanner 's , these were not entirely satisfactory from our perspective. Specifically, classification guidelines suitable for very young children were lacking. In response to the limitations of existing classification systems, we developed our own 15-scale rating system (Reichler & Schopler, 1971). These scales incorporated (a) Kanner ' s pr imary features, (b) other characteristics, noted by Creak, found
1,967 citations
TL;DR: There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.
Abstract: This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of pervasive developmental disorders (PDDs), including autistic disorder, Asperger disorder, PDD not otherwise specified, and childhood disintegrative disorder. The prevalence of autistic disorder has increased in recent surveys and current estimates of prevalence are around 20/10,000, whereas the prevalence for PDD not otherwise specified is around 30/10,000 in recent surveys. Prevalence of Asperger disorder is much lower than that for autistic disorder and childhood disintegrative disorder is a very rare disorder with a prevalence of about 2/100,000. Combined all together, recent studies that have examined the whole spectrum of PDDs have consistently provided estimates in the 60-70/10,000 range, making PDD one of the most frequent childhood neurodevelopmental disorders. The meaning of the increase in prevalence in recent decades is reviewed. There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.
1,815 citations
"Intravenous secretin for autism spe..." refers methods in this paper
...Estimates of the prevalence of ASD using the DSM-III, DSM-IIIR, DSM-IV or ICD-10 diagnostic classification systems from published synthesised literature up to April 2004 varied between 3 and 82 in 10,000 (Williams 2006), and from 2000 to 2007 between 16 and 181 in 10,000 (Fombonne 2009)....
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TL;DR: Although the indexing terms available for searching Medline for randomised clinical trials have improved, sensitivity still remains unsatisfactory.
Abstract: Objective : To examine the sensitivity and precision of Medline searching for randomised clinical trials. Design - Comparison of results of Medline searches to a “gold standard” of known randomised clinical trials in ophthalmology published in 1988; systematic review (meta-analysis) of results of similar, but separate, studies from many fields of medicine. Populations : Randomised clinical trials published in in 1988 in journals indexed in Medline, and those not indexed in Medline and identified by hand search, comprised the gold standard. Gold standards for the other studies combined in the meta-analysis were based on: randomised clinical trials published in any journal, whether indexed in Medline or not; those published in any journal indexed in Medline; or those published in a selected group of journals indexed in Medline. Main outcome measure - Sensitivity (proportion of the total number of known randomised clinical trails identified by the search) and precision (proportion of publications retrieved by Medline that were actually randomised clinical trials) were calculated for each study and combined to obtain weighted means. Searches producing the “best” sensitivity were used for sensitivity and precision estimates when multiple searches were performed. Results : The sensitivity of searching for ophthalmology randomised clinical trials published in 1988 was 82%, when the gold standard was for any journal, 87% for any journal indexed in Medline, and 88% for selected journals indexed in Medline. Weighted means for sensitivity across all studies were 51%, 77%, and 63%, respectively. The weighted mean for precision was 8% (median 32.5%). Most searchers seemed not to use freetext subject terms and truncation of those terms. Conclusion - Although the indexing terms available for searching Medline for randomised clinical trials have improved, sensitivity still remains unsatisfactory. A mechanism is needed to “register” known trials, preferably by retrospective tagging of Medline entries, and incorporating trials published before 1966 and in journals not indexed by Medline into the system.
1,810 citations