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Danielle M Wheeler

Bio: Danielle M Wheeler is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Autism & Cochrane Library. The author has an hindex of 8, co-authored 20 publications receiving 635 citations. Previous affiliations of Danielle M Wheeler include Children's Hospital at Westmead & University of Sydney.

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TL;DR: It is uncertain whether the identification and treatment of children with VUR confers clinically important benefit, and the additional benefit of surgery over antibiotics alone is small at best.
Abstract: Aims: To evaluate the benefits and harms of treatments for vesicoureteric reflux in children. Methods: Meta-analyses of randomised controlled trials using a random effects model. Main outcome measures were incidence of urinary tract infection (UTI), new or progressive renal damage, renal growth, hypertension, and glomerular filtration rate. Results: Eight trials involving 859 evaluable children comparing long term antibiotics with surgical correction of reflux (VUR) and antibiotics (seven trials) and antibiotics compared with no treatment (one trial) were identified. Risk of UTI by 1–2 and 5 years was not significantly different between surgical and medical groups (relative risk (RR) by 2 years 1.07; 95% confidence interval (CI) 0.55 to 2.09, RR by 5 years 0.99; 95% CI 0.79 to 1.26). Combined treatment resulted in a 60% reduction in febrile UTI by 5 years (RR 0.43; 95% CI 0.27 to 0.70) but no concomitant significant reduction in risk of new or progressive renal damage at 5 years (RR 1.05; 95% CI 0.85 to 1.29). In one small study no significant differences in risk for UTI or renal damage were found between antibiotic prophylaxis and no treatment. Conclusion: It is uncertain whether the identification and treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.

189 citations

Journal ArticleDOI
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.

125 citations

Reference EntryDOI
TL;DR: There is no evidence that single or multiple dose intravenous secretin is effective and as such it should not currently be recommended or administered as a treatment for autism.
Abstract: BACKGROUND Secretin is a gastro-intestinal hormone which has been presented as an effective treatment for autism based on anecdotal evidence. OBJECTIVES To determine if intravenous secretin:1. improves the core features of autism (social interaction, communication and behaviour problems); 2. improves the non-core aspects of behaviour or function such as self injurious behaviour;3. improves the quality of life of affected individuals and their carers; 4. has short term and long term effects on outcome; 5. causes harm. SEARCH STRATEGY Results of electronic searches of CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, ERIC, HealthStar and Sociofile (1998 - March 2005) were independently examined by two authors. Reference lists of trials and reviews were searched; experts and trialists were contacted to find unpublished studies. SELECTION CRITERIA Randomised controlled trials of intravenous secretin comparing secretin with a placebo treatment in children or adults diagnosed with autism spectrum disorders, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS Fourteen studies met inclusion criteria. All outcome data were continuous. Where trials used cross-over designs, analysis was conducted on results from first treatment phase, allowing combined analysis with parallel design trials. Where standardised assessment tools generated scores as outcome measures, comparisons were made between means of these scores. Where baseline means were reported, differences between treatment and control were determined to assess possible bias. Where mean change from baseline was reported, this was used in preference to post-treatment scores for meta-analyses or forest plots. As meta-analysis was possible for only one outcome (Childhood Autism Rating Scale), it was impossible to use sensitivity or subgroup analyses to assess 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 Twenty-five established standardised outcome measures were reported to assess core features of autism, communication, behaviour, visio-spatial skills, affect and adverse events within fourteen included studies. No more than four studies used any one outcome measure similarly. Outcomes were reported between three and six weeks. RCTs of efficacy of secretin in autism have not shown improvements for core features of autism. AUTHORS' CONCLUSIONS There is no evidence that single or multiple dose intravenous secretin is effective and as such it should not currently be recommended or administered as a treatment for autism. Further experimental assessment of secretin's effectiveness for autism can only be justified if methodological problems of existing research can be overcome.

71 citations

Journal Article
TL;DR: DMSA, particularly the planar technique, performs well for the diagnosis of acute pyelonephritis and SPECT DMSA alone has not been shown to be preferable to the established planar method and will result in a small number of true-positive at the expense of a larger number of false-positives.
Abstract: UNLABELLED The purpose of this study was to evaluate the performance of dimercaptosuccinic acid (DMSA) scintigraphy in the diagnosis of acute pyelonephritis and to compare the test performance of the standard technique, planar DMSA, with the newly introduced technique, SPECT DMSA. METHODS All published animal studies in which DMSA scintigraphy was compared with histopathology, the reference standard for acute pyelonephritis, were identified using a comprehensive search strategy with the MEDLINE and EMBASE databases. Test performances of all DMSA methods and SPECT versus planar DMSA were analyzed using summary receiver operating characteristic (sROC) curves. RESULTS Seven studies were identified, including 2 of SPECT DMSA. Problems in study design or reporting were common, with numerical errors in 4 studies. Overall, at a sensitivity of 86%, specificity was estimated to be 91%. Detection of acute pyelonephritis was at a lower threshold for SPECT than for planar DMSA (sensitivity/specificity values of 97%0/66% compared with 82%/ 97%), and the overall test performance of SPECT was not demonstrably better than that of planar DMSA. When applied to a group of children with a prevalence of renal damage of 40%, this means that 98% of children with abnormal planar DMSA scans will have renal damage, whereas only 65% of those with abnormal SPECT scans will have renal damage. Planar and SPECT DMSA will miss 11% and 3% of children with renal damage, respectively. Out of 100 children in the hypothetical group with 40% experiencing renal damage, SPECT will identify 6 extra true cases of renal damage at the expense of 19 extra false positives, when compared with planar DMSA. CONCLUSION Published studies of DMSA test performance are few in number and have significant methodologic problems that should be avoided in future studies. DMSA, particularly the planar technique, performs well for the diagnosis of acute pyelonephritis. Using test performance criteria, SPECT DMSA alone has not been shown to be preferable to the established planar method and will result in a small number of true-positives at the expense of a larger number of false-positives.

69 citations

Journal ArticleDOI
TL;DR: There is not sufficient evidence to support the use of auditory integration training in people with autism spectrum disorders, according to a systematic review of randomised controlled trials of adults or children with ASD.
Abstract: Objectives: To determine the effectiveness of auditory integration training (AIT) or other methods of sound therapy in people with autism spectrum disorders (ASD). Study design: A systematic review was carried out of randomised controlled trials (RCTs) of adults or children with ASD. Meta-analysis was attempted. Results: Six RCTs of AIT, including one crossover trial, were identified, with a total of 171 participants aged 3–39 years. 17 different outcome measures were used, with only two outcome measures used by three or more studies. Meta-analysis was not possible owing to very high heterogeneity or presentation of data in unusable forms. Three studies did not show any benefit of AIT over control conditions. Three studies reported improvements at 3 months in the AIT group for total mean scores of the Aberrant Behaviour Checklist (ABC), which is of questionable validity. Of these, one study also reported improvements at 3 months in the AIT group for ABC subgroup scores. No significant adverse effects of AIT were reported. Conclusion: At present there is not sufficient evidence to support its use.

66 citations


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01 Dec 2007-BMJ

1,096 citations

Journal ArticleDOI
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

Journal ArticleDOI
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

Journal ArticleDOI
TL;DR: After 1 year of follow-up monitoring, mild/moderate VUR does not increase the incidence of UTI, pyelonephritis, or renal scarring after acute pyel onephritis and a role for urinary antibiotic prophylaxis in preventing the recurrence of infection and the development of renal scars is not supported by this study.
Abstract: OBJECTIVES.To evaluate the role of primary vesicoureteral reflux (VUR) in increasing the frequency and severity of urinary tract infections (UTIs) and renal parenchymal damage among patients with acute pyelonephritis and to determine whether urinary antibiotic prophylaxis reduces the frequency and/or severity of UTIs and/or prevents renal parenchymal damage among patients with mild/moderate VUR. METHODS.Patients 3 months to 18 years of age with acute pyelonephritis, with or without VUR, were assigned randomly to receive urinary antibiotic prophylaxis or not. Patients were monitored every 3 months for 1 year. Dimercaptosuccinic acid renal scans were repeated at 6 months or if there was a recurrence of febrile UTI. Urinalysis and urine culture were performed at each clinic visit. Renal ultrasound scans and voiding cystourethrograms were repeated at the end of 1 year of follow-up monitoring. RESULTS.Of the 236 patients enrolled in the study, 218 completed the 1-year follow-up monitoring. Groups were similar with respect to age, gender, and reflux grade distribution for those with VUR. No statistically significant differences were found among the groups with respect to rate of recurrent UTI, type of recurrence, rate of subsequent pyelonephritis, and development of renal parenchymal scars. CONCLUSIONS.After 1 year of follow-up monitoring, mild/moderate VUR does not increase the incidence of UTI, pyelonephritis, or renal scarring after acute pyelonephritis. Moreover, a role for urinary antibiotic prophylaxis in preventing the recurrence of infection and the development of renal scars is not supported by this study.

536 citations

Journal ArticleDOI
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