Deborah A. Pearson

ZIDOVUDINE, DIDANOSINE, OR BOTH AS THE INITIAL TREATMENT FOR SYMPTOMATIC HIV-INFECTED CHILDREN

BACKGROUND Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine. METHODS In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or > or =30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease. RESULTS Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036). CONCLUSIONS In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.

Emotion recognition in autism: Verbal and nonverbal information

This study examined the roles of verbal and nonverbal sources of information in the ability of persons with and without autism to recognize emotion. Child, adolescent, and young adult participants in four groups [Lower Functioning Autism (LFA) (n = 17), High Functioning Autism (HFA) (n = 18), Lower Functioning Comparison (LFC) (n = 18), and High Functioning Comparison (HFC) (n = 23)] identified emotions shown (happy, angry, sad, surprised, or neutral) in video clips of individuals expressing emotion verbally, nonverbally, or both. Verbal expressions of emotion were either Explicit, Implicit, or Neutral, whereas nonverbal expressions were Animate or Flat (3 x 2). Pairwise ANCOVAs indicated no group differences between HFA and HFC groups or between the LFA and LFC groups, and indicated instead group differences between higher and lower functioning persons. With groups collapsed into High Functioning (HF) and Lower Functioning (LF), significant group differences were found. Performance of LF individuals suggested they had difficulty inferring how a person felt based on what the person said, if the emotion was not explicitly named. Performance of HF individuals suggested they relied more on nonverbal than on verbal information to determine a speakers emotion, except where the emotion was explicitly named. Results suggested that persons with autistic spectrum disorders can use affective information from multiple sources in much the same ways as persons of comparable developmental level without autism.

Imitation and expression of facial affect in autism

This study examined elicited (posed) affective expressions in children, adolescents, and young adults with autism ( N = 18) or Downs syndrome ( N = 24). Subjects were asked to (a) imitate five modeled expressions (Imitation task) and (b) produce five labeled expressions (Expression task). Subjects with autism produced recognizable expressions in both tasks, but they produced fewer than did subjects with Downs syndrome when target emotions were labeled but not modeled (Expression). Imitation and Expression tasks were equally difficult for subjects with autism, but subjects with Downs syndrome performed better in Expression than in Imitation. In both tasks, the responses of subjects with autism contained many unusual behaviors, such as bizarre expressions and those that looked “mechanical.” Results suggest that producing elicited affective expressions is more difficult for persons with autism than for persons with Downs syndrome of similar chronological age, mental age, and IQ.

Altered brain activation during cognitive control in patients with moderate to severe traumatic brain injury.

Background. Persistent deficits in cognitive control have been documented following traumatic brain injury (TBI) but are inconsistently related to the presence and location of focal lesions. Objective. Functional magnetic resonance imaging (fMRI) was used to examine brain activation during a cognitive control task in patients with moderate to severe TBI or orthopedic injury (OI). Methods. Fourteen TBI patients and 10 OI patients underwent fMRI at 3 months postinjury using a stimulus-response compatibility task in which response accuracy and reaction time were measured. Performance between the groups was equated by individually adjusting the amount of training. Groups did not differ in age, gender, or education. Results. Brain activation during stimulus-response incompatibility was greater in TBI patients than in OI patients within the cingulate, medial frontal, middle frontal, and superior frontal gyri. However, the positive regression of activation with response accuracy during stimulus-response incompatibility indicated a stronger relationship for OI patients than the TBI group within the anterior cingulate gyrus, medial frontal, and parietal regions, as well as deep brain structures (eg, brainstem). The number of focal lesions within either the whole brain or within prefrontal areas was not related to brain activation, but there was a relationship between activation and TBI severity. Conclusions. These findings suggest that neural networks mediating cognitive control are altered after moderate to severe TBI, possibly as a result of diffuse axonal injury, and that the typical relationship of brain activation to performance is disrupted.

Measuring Anxiety as a Treatment Endpoint in Youth with Autism Spectrum Disorder

Despite the high rate of anxiety in individuals with autism spectrum disorder (ASD), measuring anxiety in ASD is fraught with uncertainty. This is due, in part, to incomplete consensus on the manifestations of anxiety in this population. Autism Speaks assembled a panel of experts to conduct a systematic review of available measures for anxiety in youth with ASD. To complete the review, the panel held monthly conference calls and two face-to-face meetings over a fourteen-month period. Thirty eight published studies were reviewed and ten assessment measures were examined: four were deemed appropriate for use in clinical trials, although with conditions; three were judged to be potentially appropriate, while three were considered not useful for clinical trials assessing anxiety. Despite recent advances, additional relevant, reliable and valid outcome measures are needed to evaluate treatments for anxiety in ASD.

A comparison of behavioral and emotional functioning in children and adolescents with Autistic Disorder and PDD-NOS

Behavioral symptomatology was compared in 26 children and adolescents with Autistic Disorder (“autism”) and 25 children and adolescents with Pervasive Developmental Disorder, Not Otherwise Specified (“PDD-NOS”). Relative to individuals with PDD-NOS, those with autism had more symptoms of depression, social withdrawal, atypical behavior, and immature social skills—and fewer family problems. These differences remained even when group differences in intellectual ability were statistically controlled. No group differences emerged in somatization, anxiety, or hyperactivity. Findings suggest that although both groups demonstrate considerable evidence of behavioral and emotional problems, those with autism are at particularly high risk for comorbid behavioral and emotional disabilities.

Judgments of Social Appropriateness by Children and Adolescents with Autism.

Children and adolescents with autism (autism group, n = 19) and those without autism (Nonautism group, n = 19) of similar age and IQ were asked to make judgments of the social appropriateness of 24 videotaped, staged scenes with adult actors. Each scene depicted an appropriate or an inappropriate interaction. Half contained verbalizations, and half did not. After each scene, the participant was asked: (1) Was that o.k. or was something wrong with it? If the participant judged the scene was wrong, she or he was asked: (2) What was wrong with it?; and (3) Why was that wrong? Both groups correctly identified inappropriate behaviors most of the time, and correct behaviors almost all of the time. However, the Nonautism group detected inappropriate behaviors significantly more often than the Autism group, for verbal but not nonverbal scenes. It was also significantly easier for both groups to identify inappropriate behaviors in the nonverbal than in the verbal scenes. Ratings of the explanations given for Question 3 differed significantly between the groups for verbal but not for nonverbal scenes, with Nonautism participants more likely to give explanations involving social norms and principles, and the Autism group more likely to give explanations that were irrelevant or idiosyncratic.

An fMRI study of executive functioning after severe diffuse TBI.

Primary objective: Preliminary study of whether severe diffuse traumatic brain injury (TBI) increases extent of frontal tissue recruited by cognitive control tasks. Research design: Functional magnetic resonance imaging (fMRI) on N-back working memory (WM) and arrows inhibition tasks in a 46 year old man who had severe diffuse TBI 1 year earlier, a 44 year old man (inhibition task) and three women (working memory task), age 20-26 years. Images were acquired by 1.5 T magnet with BOLD method and PRESTO pulse sequence and analysed using SPM. Main outcomes and results: Frontal activation increased under 2-back relative to 1-back condition of working memory in all participants with more extensive activation in the TBI patient relative to controls. Frontal activation increased with inhibition on the arrows task, but was greater in the TBI patient. Conclusion: Severe diffuse TBI results in recruitment of additional neural resources for cognitive control.

Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children

BackgroundA large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related disti

Fronto-Limbic Functioning in Children and Adolescents with and without Autism.

We used neuropsychological tasks to investigate integrity of brain circuits linking orbitofrontal cortex and amygdala (orbitofrontal-amygdala), and dorsolateral prefrontal cortex and hippocampus (dorsolateral prefrontal-hippocampus), in 138 individuals aged 7-18 years, with and without autism. We predicted that performance on orbitofrontal-amygdala tasks would be poorer in the Autism group compared to the Non-Autism group regardless of intellectual level (verbal mental age, VMA) and that performance on dorsolateral prefrontal-hippocampus tasks would be associated primarily with intellectual level. Predicted differences between Autism and Non-Autism groups on orbitofrontal-amygdala tasks were present but greater in individuals with higher VMA. On dorsolateral prefrontal-hippocampus tasks, poorer performance by the Autism compared to the Non-Autism group was found at all VMA levels. Group differences suggest both brain circuits are impaired in autism, but performance on all tasks is also associated with intellectual level.