Are Children Severely Affected by Autism Spectrum Disorder Underrepresented in Treatment Studies? An Analysis of the Literature.

Despite significant advances in autism research, experts have noted that children severely affected by autism spectrum disorder (ASD) appear to have been understudied. Rigorous analysis of this observation has been limited, and the representation of severity has not been well-described. We assessed three domains of severity (communication ability, cognitive functioning, and adaptive functioning) in 367 treatment studies of children with ASD published 1991-2013. We found that the proportion of studies that included the severely affected population decreased significantly over time, as well as wide variability in measurement and reporting. Inadequate representation of the full autism spectrum in the literature could lead to an unbalanced picture of ASD and leave behind those with arguably the greatest need.

Predicting Imminent Aggression Onset in Minimally-Verbal Youth with Autism Spectrum Disorder Using Preceding Physiological Signals.

We test the hypothesis that changes in preceding physiological arousal can be used to predict imminent aggression proximally before it occurs in youth with autism spectrum disorder (ASD) who are minimally verbal (MV-ASD). We evaluate this hypothesis through statistical analyses performed on physiological biosensor data wirelessly recorded from 20 MV-ASD youth over 69 independent naturalistic observations in a hospital inpatient unit. Using ridge-regularized logistic regression, results demonstrate that, on average, our models are able to predict the onset of aggression 1 minute before it occurs using 3 minutes of prior data with a 0.71 AUC for global, and a 0.84 AUC for person-dependent models.

Pediatric Professional Medical Associations and Industry Guideline Compliance.

BACKGROUND AND OBJECTIVES: There has been an increasing focus on the relationship between pediatric prescribers and the biomedical industry. There is a lack of research, however, on the biomedical industry's relationship with the professional medical associations (PMAs) of pediatric prescribers. We developed a systematic method to assess this relationship by evaluating PMA transparency and compliance with a set of 2009 best practice guidelines (BPGs). METHODS: Nine PMAs rated as having the greatest influence on pediatric prescribers were examined. Two researchers independently coded publicly accessible information from the PMAs' Web sites for transparency and compliance with 36 BPG recommendations. Using the coded data, an industry relationship index (IRI) score was developed to systematize comparisons across PMAs. RESULTS: The PMAs demonstrated transparency and compliance with less than one-half of the 2009 BPGs (mean ± SD: 30.2 ± 15.6; range: 8-51 on the 66-point IRI scale). Two PMAs clustered in the high IRI (more transparent and compliant) group, 3 in the medium group, and 4 in the low group. There was no significant association of IRI group status and the PMAs' number of members or age. PMAs were least compliant with recommendations that prohibit or limit financial relationships with industry. CONCLUSIONS: PMAs with influence on pediatric prescribers have achieved only limited transparency and compliance with a set of 2009 BPGs, particularly with respect to financial separation from industry. Use of quantifiable standards of conduct facilitates comparisons between organizations and may enhance public trust in PMAs, preserving their ability to achieve organizational goals.

Preliminary investigation of lithium for mood disorder symptoms in children and adolescents with autism spectrum disorder.

OBJECTIVE: Children with autism spectrum disorder (ASD) have higher rates of comorbid psychiatric disorders, including mood disorders, than the general child population. Although children with ASD may experience irritability (aggression, self-injury, and tantrums), a portion also experience symptoms that are typical of a mood disorder, such as euphoria/elevated mood, mania, hypersexuality, paranoia, or decreased need for sleep. Despite lithium's established efficacy in controlling mood disorder symptoms in the neurotypical population, lithium has been rarely studied in children with ASD. METHODS: We performed a retrospective chart review of 30 children and adolescents diagnosed with ASD by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria who were prescribed lithium in order to assess target symptoms, safety, and tolerability. Clinical Global Impressions - Improvement (CGI-I) ratings were performed by two board-certified child psychiatrists with expertise in ASD. CGI-I scores were dichotomized into "improved" (CGI-I score of 1 or 2) or "not improved" (CGI-I score ≥3). RESULTS: Forty-three percent of patients who received lithium were rated as "improved" on the CGI-I. Seventy-one percent of patients who had two or more pretreatment mood disorder symptoms were rated as "improved." The presence of mania (p=0.033) or euphoria/elevated mood (p=0.041) were the pretreatment symptoms significantly associated with an "improved" rating. The mean lithium blood level was 0.70 mEq/L (SD=0.26), and the average length of lithium treatment was 29.7 days (SD=23.9). Forty-seven percent of patients were reported to have at least one side effect, most commonly vomiting (13%), tremor (10%), fatigue (10%), irritability (7%), and enuresis (7%). CONCLUSIONS: This preliminary assessment of lithium in children and adolescents with ASD suggests that lithium may be a medication of interest for those who exhibit two or more mood disorder symptoms, particularly mania or euphoria/elevated mood. A relatively high side effect rate merits caution, and these results are limited by the retrospective, uncontrolled study design. Future study of lithium in a prospective trial with treatment-sensitive outcome measures may be indicated.