Efficacy of a Remote Play-Based Intervention for Children With Prader-Willi Syndrome.

The current study examines the efficacy of an 8-week pretend play intervention targeting social-cognitive abilities in children with Prader-Willi syndrome (PWS), ages 6-9. PWS is a rare disorder associated with various social, emotional, and cognitive challenges linked to pretend play impairments, and for which interventions are sparse. Nineteen children were quasi-randomized to receive the intervention or be part of a waitlist control group. Participants who received the intervention (n = 10) demonstrated significant improvements in various components of pretend play, most notably in organization of play, which may generalize to broader social-cognitive gains. These findings provide evidence of the intervention's efficacy in enhancing pretend play skills and related social-cognitive abilities during this critical period of development for children with PWS.

Neural correlates of inhibitory control in severe class III compared with class I/II obesity using a sample of endometrial cancer survivors seeking weight loss.

OBJECTIVE: No prior studies have evaluated inhibitory control in people with severe class III compared with class I/II obesity. Thus, the study aim was to evaluate inhibitory control and neural correlates of response inhibition by obesity class using a sample of endometrial cancer (EC) survivors with obesity, who have a higher risk of overall but not cancer-specific mortality. METHODS: Forty-eight stage I EC survivors with obesity (class I/II: n = 21; class III: n = 27) seeking weight loss in a lifestyle intervention at baseline completed a stop signal task during functional magnetic resonance imaging. RESULTS: It was found that participants with class III obesity had a longer stop signal reaction time (mean [SD], 278.8 [51.3] vs. 251.5 [34.0] milliseconds, p < 0.01) compared with those with class I/II obesity, indicating that patients with EC with severe obesity had greater impulsivity and poorer inhibitory control. Results also showed increased activation in the thalamus and superior frontal gyrus for the incorrect versus correct inhibition contrast in class III but not class I/II obesity (whole brain cluster corrected, p < 0.05). CONCLUSIONS: These results provide novel insights into inhibitory control and corresponding neural correlates in severe versus less severe classes of obesity and highlight the importance of targeting inhibitory control processes in weight-loss interventions, particularly for people with severe obesity and greater impulsivity.

The Autism Symptom Dimensions Questionnaire: Development and psychometric evaluation of a new, open-source measure of autism symptomatology.

AIM: To describe the development and initial psychometric evaluation of a new, freely available measure, the Autism Symptom Dimensions Questionnaire (ASDQ). METHOD: After development and revision of an initial 33-item version, informants completed a revised 39-item version of the ASDQ on 1467 children and adolescents (aged 2-17 years), including 104 with autism spectrum disorder (ASD). RESULTS: The initial 33-item version of the ASDQ had good reliability and construct validity. However, only four specific symptom factors were identified, potentially due to an insufficient number of items. Factor analyses of the expanded instrument identified a general ASD factor and nine specific symptom factors with good measurement invariance across demographic groups. Scales showed good-to-excellent overall and conditional reliability. Exploratory analyses of predictive validity for ASD versus neurotypical and other developmental disability diagnoses indicated good accuracy for population and at-risk contexts. INTERPRETATION: The ASDQ is a free and psychometrically sound informant report instrument with good reliability of measurement across a continuous range of scores and preliminary evidence of predictive validity. The measure may be a useful alternative to existing autism symptom measures but further studies with comparison of clinical diagnoses using criterion-standard instruments are needed. WHAT THIS PAPER ADDS: The Autism Symptom Dimensions Questionnaire (ASDQ) is a new, freely available measure of autism symptoms. The ASDQ showed reliable and accurate measurement of autism symptoms. The measure had good screening efficiency for autism spectrum disorder relative to other developmental conditions.

Improving Surveillance and Epidemic Response in Ohio Childcare Settings.

At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021. Additionally, active surveillance with self-administered reverse transcriptase-polymerase chain reaction (RT-PCR) tests were conducted among staff at 46 childcare programs. Finally, six zoom-based focus groups with program administrators were used to gain feedback. Staff and children in childcare settings contributed 0.38% and 0.15% of the COVID-19 cases in Ohio during this timeframe, respectively. RT-PCR testing identified 3 unrecognized cases (0.88% of tests), and all occurred when the statewide positivity rate was >5%. Focus groups revealed that access to affordable cleaning supplies, masks, and reliable staffing were critical. Perhaps most importantly, we conclude that expanding the incident reporting system to include a childcare census would allow for the tracking of future health problems with highly valuable incidence rate estimations.

Intervention Response by Genetic Subtype: PRETEND-Preschool Program for Children with Prader-Willi Syndrome via Remote Parent Training.

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder associated with social cognitive challenges, and pretend play has been demonstrated as a tool to achieve developmental goals. Following previous report on feasibility and acceptability of a remote, play-based parent-training program (Zyga, Russ, & Dimitropoulos, 2018), we now report on preliminary efficacy of this program to enhance pretend play skills and social cognitive skills in preschoolers with PWS. Results across two studies demonstrated efficacy when live-coaching play sessions incorporated children into the intervention. Increases in play skills were observed for children with the mUPD subtype of PWS who underwent intervention, compared with children with mUPD who were waitlisted. Children with DEL subtype were less likely to respond to intervention. Implications for results are discussed.

Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org ) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC "Behavior Outcomes Working Group" sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive-compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.

Believing in Make-Believe: Efficacy of a Pretend Play Intervention for School-Aged Children with High-Functioning Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by socio-emotional deficits, and difficulties with pretend play skills. Play skills are related to processes of adaptive functioning and emotion understanding. The present pilot study implemented an in-person pretend play intervention to school-aged children (ages 6 to 9 years, intervention group = 18, control group = 7) diagnosed with high-functioning ASD (HF-ASD), to increase children's cognitive and affective play skills, and emotional understanding abilities. The intervention consisted of 5 weekly sessions, 15-20 minutes each. The intervention group significantly increased in imagination and cognitive play skills, which generalized to increased skills in emotional understanding. Findings demonstrate the positive impact of a short, easily facilitated, accessible play intervention for school-aged children with HF-ASD.

Show me what happens next: Preliminary efficacy of a remote play-based intervention for children with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is characterized by decreased social and emotional functioning. Due to the low base-rate of children with PWS, developing behavioral interventions for individuals with PWS is faced with the challenge of enrolling enough local participants for adequate study of behavioral intervention efficacy. However, these types of studies are greatly needed in PWS and telehealth methodology may be useful in addressing this challenge. This article is a follow-up to a previous feasibility study (Dimitropoulos et al., 2017) and reports on the preliminary efficacy of a telehealth intervention delivered to 15 children, ages 6-12, with PWS. Overall, children demonstrated significantly improved cognitive and affective processes in pretend play and general cognitive flexibility following the 6-week remote intervention. These findings are limited by the lack of control group and small sample size which should be considered when interpreting results. Overall, these preliminary findings point to the potential role pretend play can serve as a means of enacting cognitive and behavioral change via telehealth.

Insights to the neural response to food cues in class III compared with class I and II obese adults using a sample of endometrial cancer survivors seeking weight loss.

BACKGROUND: The rates of severe or Class III obesity (BMI ≥ 40.0 kg/m2) and endometrial cancer (EC) incidence and mortality have been increasing significantly in the United States. Adults with severe obesity are more likely to die and women with severe obesity have a higher risk of EC development and mortality than those with Class I/II obesity (BMI: 30-<40 kg/m2). However, no prior studies have evaluated the neural response to food cues by obesity severity/class in adults with or without cancer. METHODS: We conducted a functional magnetic resonance imaging visual food cue task in 85 obese Stage I EC survivors who were seeking weight loss in a lifestyle intervention at baseline. We evaluated the neural response to high-calorie vs. non-food images after an overnight fast (fasted state) and after eating a standardized meal (fed state), and grouped patients by obesity class (Class I/II: n = 38; Class III: n = 47). RESULTS: In the fasted state, we found increased activation in several regions including the dorsolateral prefrontal cortex (DLPFC) in Class III and Class I/II patients (whole brain cluster corrected (WBCC), p < 0.05), which was significantly higher in Class III vs. Class I/II (p < 0.05). We found decreased activation in the insula in the fasted state, which was significantly lower in Class I/II vs. Class III (p = 0.03). In the fed state, we found increased activation in the DLPFC in Class III and Class I/II (WBCC, p < 0.05). The increased activation in cognitive control/inhibition regions (DLPFC) is consistent with the summative literature; however, the decreased activation in taste information processing regions (insula) was unexpected. CONCLUSIONS: Our results provide novel insights on food cue response between different classes of obesity and highlight the importance of targeting the DLPFC in weight loss interventions, particularly in severely obese patients. Additional studies examining food-related neural circuitry between different classes of obesity are needed.

Eye tracking as an objective measure of hyperphagia in children with Prader-Willi syndrome.

This study examined sensitivity of eye tracking measures to hyperphagia severity in Prader-Willi syndrome (PWS). Gaze data were collected in 57 children with PWS, age 3-11 years, and 47 typically developing peers at two study sites during free visual exploration of complex stimulus arrays that included images of food, animals, and household objects. Analysis of the number and duration of fixations as well as gaze perseverations revealed that food items are not exceptionally salient for children with PWS. Instead, increased attention to food in the context of other high-interest items (e.g., animals) was associated with caregiver reports of more severe hyperphagia and more advanced nutritional phase. The study also provided preliminary evidence of possible genetic subtype and sex differences as well as demonstrated that multiple investigators in a wide range of settings can effectively implement the eye tracking protocol. The results indicate that gaze characteristics derived from eye tracking may be a promising objective marker of hyperphagia in PWS for use in research and clinical trials.

Sleep, quality of life, and depression in endometrial cancer survivors with obesity seeking weight loss.

PURPOSE: Incidence and mortality rates of uterine cancer are increasing and, obesity, which is also rising, has been associated with uterine cancer development and mortality. A recent study found that poor sleep quality is common among endometrial cancer survivors and those with obesity had more sleep disturbances than those having normal weight. However, it is unclear if higher levels of obesity (Class III, BMI ≥ 40 kg/m2), which are rising rapidly, are differentially associated with sleep as well as depression and quality of life in endometrial cancer survivors. METHODS: We evaluated sleep, depression, and quality of life in 100 Stage I endometrial cancer survivors with obesity seeking weight loss enrolled in a lifestyle intervention (NCT01870947) at baseline. RESULTS: The average age was 60 years and mean BMI was 42.1 kg/m2 with 58% having a BMI ≥ 40 kg/m2. Most survivors (72.3%) had poor sleep quality and most (71.2%) reported sleeping < 7 h/night. Survivors with class III compared with class I obesity had significantly more sleep disturbances and daytime dysfunction; and, those with poor sleep had higher depression and lower quality of life. Survivors with a BMI ≥ 50 kg/m2 (~ 25%) had the highest levels of depression and lowest physical and emotional well-being. CONCLUSIONS: Our results reveal that endometrial cancer survivors with class III compared with class I obesity have poorer sleep quality, higher depression, and lower quality of life. Given the rising rates of obesity and uterine cancer mortality, interventions to combat both obesity and poor sleep are needed.

Preliminary Characterization of Parent-Child Interaction in Preschoolers With Prader-Willi Syndrome: The Relationship Between Engagement and Parental Stress.

Early parent-child interactions (PCI) impact social cognitive development. Relatedly, children with various developmental disorders exhibit abnormal parental attachment relationships. Parental characteristics and behaviors can impact PCI and socioemotional development as well. No research has examined the parent-child dynamic in Prader-Willi syndrome (PWS), a neurodevelopmental disorder that presents with social cognitive deficits. This article provides a preliminary characterization of PCI quality and parenting stress in 17 PWS parent-child dyads, children ages 3-5 years, in comparison to 20 typically developing children and their parent. Results suggest early PCI disruption in preschoolers with PWS and their parents report increased levels of stress in various domains. These findings have important implications not only on parent well-being in PWS but its impact on child development.

Early Social Cognitive Ability in Preschoolers with Prader-Willi Syndrome and Autism Spectrum Disorder.

Children with Prader-Willi syndrome (PWS) and autism spectrum disorder (ASD) present with challenges in social cognitive ability, Research comparing PWS to ASD is important given the implication of 15q11-q13 region in the biology of autism. However, recent findings question the accuracy of relying solely on parent report in behavioral characterization. Thus, this study examined social cognition in an observable pretend play task and by parent report in 50 preschool children (ages 3-5) with PWS, by subtype, compared to ASD. Behaviorally, the paternal deletion subtype expressed overall higher functioning, whereas the maternal uniparental disomy subtype performed more similarly to the ASD group. Results are the first to show deficits in social cognitive ability early in development. The severity and differences in deficits between PWS subtypes are important in informing early intervention efforts.

The PRETEND Program: Evaluating the Feasibility of a Remote Parent-Training Intervention for Children With Prader-Willi Syndrome.

Research has shown that children with Prader-Willi syndrome (PWS) have social-cognitive challenges and decreased quality parent-child interactions. However, given the low prevalence rate, developing interventions for children with PWS is faced with the significant challenge of enrolling enough participants for local studies. To better understand the feasibility and acceptability of telehealth, the current study delivered a 6-week remote parent training intervention to 15 primary caregivers of a child with PWS (ages 3-6). Behavioral Intervention Rating Scale results indicate good acceptability (5.64/6.00) and satisfaction (4.75/5.00) with the intervention. These results are one of the first to support the use of telehealth in conducting parent training in rare disorders, such as PWS.

Evaluating the Feasibility of a Play-Based Telehealth Intervention Program for Children with Prader-Willi Syndrome.

Here we report the feasibility and acceptability of telehealth for direct intervention in children with Prader-Willi syndrome (PWS). Children with PWS have social-cognitive challenges that are similar to children with ASD. However, developing behavioral interventions for individuals with PWS is faced with the significant challenge of enrolling enough participants for local studies where multiple visits per week are indicated for effective intervention. This study delivered a 6-week play-based intervention via telehealth directly to eight children with PWS (6-12 years). Participants completed the program with minimal behavioral or technological difficulty (#sessions M = 11.875/12). Behavioral Intervention Rating Scale results indicate good acceptability (M = 5.54/6.00). These findings support using telehealth in rare disorders and delivering intervention directly to children with developmental delays through this modality.

Sensitivity of the modified Children's Yale-Brown Obsessive Compulsive Scale to detect change: Results from two multi-site trials.

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all three active treatment groups showed significant improvement (effect sizes: 0.74-0.88). There were no differences between active treatment groups. These results indicate that the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder has acceptable test-retest as evidenced by the medium to high correlations in the placebo group and demonstrated sensitivity to change with treatment.

Can preoperative cranial ultrasound predict early neurodevelopmental outcome in infants with congenital heart disease?

AIM: To determine the role of preoperative cranial ultrasound (cUS) in predicting neurodevelopmental outcome in infants undergoing bypass surgery for congenital heart disease (CHD). METHOD: Prospective cohort study on 77 infants (44 males, 33 females) operated before 3 months of age (median age at surgery 10d [range 3-88d]) who received at least one preoperative cUS. Outcome at 1 year was assessed with a standardized neurological examination and the Bayley Scales of Infant Development II (mental developmental index [MDI]; psychomotor developmental index [PDI]). RESULTS: Abnormalities on cUS were detected in 22 (29%) infants and consisted of diffuse brain oedema (n=12, 16%), periventricular white matter injury (n=5, 6%), ventricular dilatation (n=3, 4%), and intraventricular haemorrhage (IVH) (n=2, 3%). Infants undergoing balloon-atrial septostomy (BAS) had a higher rate of subsequent brain oedema than those without BAS (p=0.006). cUS abnormalities were not related to neurodevelopmental outcome. INTERPRETATION: Preoperative cUS findings in infants undergoing bypass surgery for CHD occur rather frequently, consisting of mild lesions such as brain oedema or white matter changes. These findings, however, do not correlate with early neurodevelopmental outcome.

Assessment of pretend play in Prader-Willi syndrome: a direct comparison to autism spectrum disorder.

Children with Prader-Willi syndrome (PWS) are at risk for autism spectrum disorder (ASD), including pervasive social deficits. While play impairments in ASD are well documented, play abilities in PWS have not been evaluated. Fourteen children with PWS and ten children with ASD were administered the Autism Diagnostic Observation Schedule (ADOS) (Lord et al. in Autism Diagnostic Observation Schedule manual. Western Psychological Services, Los Angeles, 2006) as part of a larger project. A modified Affect in Play Scale (APS; Russ in Play in child development and psychotherapy: toward empirically supported practice. Lawrence Erlbaum Associates Publishers, Mahwah, 2004; Pretend play in childhood: foundation of adult creativity. APA Books, Washington, 2014) was used to score ADOS play activities. Results indicate both groups scored below normative data on measures of imagination, organization, and affective expression during individual play. In addition, the inclusion of a play partner in both groups increased all scaled scores on the APS. These findings suggest children with PWS show impaired pretend play abilities similar to ASD. Further research is warranted and should focus on constructing and validating programs aimed at improving symbolic and functional play abilities within these populations.

Rationale and design of REWARD (revving-up exercise for sustained weight loss by altering neurological reward and drive): a randomized trial in obese endometrial cancer survivors.

BACKGROUND: Obesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. "Assisted" exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. METHODS: We describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to "assisted" or voluntary rate cycling to evaluate the efficacy of "assisted" exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3 days/week of supervised exercise and 1 day/week of a group dietary behavioral intervention for 16 weeks and, then, will be followed for 6 months. OUTCOMES: The primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. CONCLUSIONS: If successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients.

Influence of feeding state on neurofunctional differences between individuals who are obese and normal weight: a meta-analysis of neuroimaging studies.

Obesity is a complex disorder associated with serious health risks. Examining differences in brain activity between normal weight and obese populations in response to food cues may help researchers and clinicians understand the underlying causes of overeating and obesity and help prevent them. Multiple neuroimaging studies have investigated weight differences in functional activity to food cues but have found varying results. We performed six meta-analyses of functional neuroimaging studies of weight differences in response to food images and isolated differences in processing between normal weight and obese participants. Within this study, 7 papers and 3 sets of unpublished data on functional activation to food images were analyzed using an Activation Likelihood Estimation meta-analytic approach. These analyses also addressed how feeding state impacts functional activity between weight groups. Feeding state affected weight related differences in neurofunctional activity triggered by visual food cues. In the premeal state, greater activation in the amygdala/hippocampus was found in obese participants compared to normal weight participants and, in the postmeal state, obese individuals had greater activation in the caudate and medial prefrontal cortex (MPFC) as compared to normal weight individuals. Regions of the brain associated with caloric evaluation, arousal, and memory were more active in the obese before eating, while less activity was found in an area linked to interoceptive processing. In the postmeal state, greater activity was found in the obese in areas related to risk vs. reward evaluation and reward processing. These findings may help researchers and clinicians understand and treat obesity related behaviors by identifying the altered functional regions that lead to obesity, providing a guide for future research on which neural regions need to be the target of further investigation.