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Background A three-pronged approach to acne treatment—combining an antibiotic, antibacterial, and retinoid—could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. Objectives We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. Methods In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. Results A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8–30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6–26.8; noninflammatory, 21.8–30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. Conclusions Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. Clinical Trial Registration ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017). Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00650-3.

PURPOSE The rho-associated coiled-coil–containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil (KD025) may offer a novel approach to the management of chronic graft-versus-host disease (cGVHD). PATIENTS AND METHODS A phase IIa, open-label, dose-finding study of belumosudil enrolled 54 patients with cGVHD who had received one to three prior lines of therapy (LOTs). The primary end point was overall response rate (ORR). RESULTS The median time from cGVHD diagnosis to enrollment was 20 months. Seventy-eight percent of patients had severe cGVHD, 50% had ≥ 4 organs involved, 73% had cGVHD refractory to their last LOT, and 50% had received ≥ 3 prior LOTs. With an overall median follow-up of 29 months, the ORR (95% CI) with belumosudil 200 mg once daily, 200 mg twice daily, and 400 mg once daily was 65% (38% to 86%), 69% (41% to 89%), and 62% (38% to 82%), respectively. Responses were clinically meaningful, with a median duration of response of 35 weeks, and were associated with quality-of-life improvements and corticosteroid (CS) dose reductions. CS treatment was discontinued in 19% of patients. The failure-free survival rate was 76% (62% to 85%) and 47% (33% to 60%) at 6 and 12 months, respectively. The 2-year overall survival rate was 82% (69% to 90%). Belumosudil was well-tolerated, with low rates of cytopenia. There were no unexpected adverse events and no apparent increased risk of infection, including cytomegalovirus infection and reactivation. CONCLUSION Belumosudil treatment resulted in a high ORR and overall survival rate and demonstrated quality-of-life improvements, CS dose reductions, and limited toxicity. Data from the study indicated that belumosudil may prove to be an effective therapy for patients with treatment-refractory cGVHD.

Families often face financial and geographical barriers to services for children with autism. The current study explored the effectiveness of a parent-supported adaptation of the computer game-based social skills program Secret Agent Society (SAS). Seventy child-parent dyads were randomized to SAS (n = 35) or a caregiver-supported cognitive skills training game (CIA—control comparison; n = 35), both completed over 10 weeks. Child participants were on the autism spectrum and aged seven to 12 years (60 boys, 10 girls). SAS participants improved more than CIA participants on parent-rated social skills and problem behaviors and teacher-rated social skills. Findings suggest the intervention may be a convenient, cost-effective therapeutic approach, especially during times of restricted face-to-face service access, such as COVID-19.

Modern advances in technology such as next-generation sequencing and digital PCR make detection of minor circulating cell-free tumor DNA amounts in blood from cancer patients possible. Samples can be obtained minimal-invasively, tested for treatment-determining genetic alterations and are considered to reflect the genetic constitution of the whole tumor mass. Furthermore, tumor development can be determined by a time course of the quantified circulating cell-free tumor DNA. However, systematic studies which prove the clinical relevance of monitoring patients using liquid biopsies are still lacking. In this study, we collected 115 samples from 47 late stage melanoma patients over 1.5 years alongside therapy-associated clinical routine monitoring. Mutation status was confirmed by molecular analysis of primary tumor material. We can show that detectable levels of circulating cell-free tumor DNA correlate with clinical development over time. Increasing levels of circulating cell-free tumor DNA during melanoma treatment with either targeted therapy (BRAF/MEK inhibitors) or immunotherapy, during recovery time or the intervals between last treatment cycle and second-line treatment point towards clinical progression before the progression becomes obvious in imaging. Therefore, this is a further possibility to closely screen our patients for tumor progression during therapy, in therapy-free phases and in earlier stages before therapy initiation.

Introduction Adolescents with intellectual and/or developmental disabilities (IDD) are at high risk for sexual exploitation, yet there is a paucity of research on their romantic relationships. The objectives of this study were to examine the romantic understanding and experiences of youth with IDD. Methods Thirty-one adolescents (16–19 years; 21 males and 10 females) with IDD (12 participants with additional diagnosis of ASD) were recruited from a community health clinic. Individual interviews and questionnaires assessed cross-sectionally these youths’: (1) romantic conceptualizations; (2) romantic awareness (knowledge of: romantic relationships, sexual behaviours, initiating relationships); (3) involvement; (4) social competence; and (5) expectations for autonomy. Parent perspectives on these topics were also captured through questionnaires. Results While 85% reported an immediate desire for a romantic relationship, only 35% were currently in a relationship. Qualitative findings indicated that 14% of youth were unable to differentiate between a romantic relationship and a friendship. Among those who could make this distinction, romantic relationships were conceptualized as serious, commitment for life, and primarily for companionship. Adolescents with ASD, compared to those without ASD, showed weaker social competence and lower romantic awareness. Parents were adolescents’ primary source of information about relationships. Finally, parents and adolescents differed in their perception of the age at which they were ready to date. Conclusions This study contributes to our understanding of the romantic experiences of youth with IDD. Prevention efforts focused on education may be important to help ensure these youth develop safe and healthy relationships.

Therapeutic alliance (TA), or the collaborative relationship between a therapist and client, has been shown to be an important component of intervention success. The objective of this study was to examine the psychometric properties of the Therapy Process Observational Coding System-Alliance Scale (TPOCS-A). The sample consisted of 20 children (19 males) ages 8 to 12 years with autism and their parents (15 mothers, 5 fathers), who completed a cognitive-behavioural intervention designed to improve children's emotion regulation skills. Two trained coders rated early, middle, and late parent and child alliance using the TPOCS-A after watching video recorded therapy sessions. Therapist-reported child involvement, alliance, and adherence were also assessed. Psychometric findings revealed that the TPOCS-A is a reliable and valid measure of therapeutic alliance for children with autism. The implications of examining TA in empirically supported treatments for this population are discussed.

Background Acne affects more than 80% of adolescents and young adults, who most often develop acne scars. Supporting data on the effect of acne scars on patient’s health-related quality of life (HRQOL) are limited. Objective The aim was to determine how the severity of acne scars impacts the HRQOL of afflicted individuals. Methods In this population-based cross-sectional study, 723 adults with facial acne scars but without active acne lesions self-completed the Self-assessment of Clinical Acne-Related Scars (SCARS) questionnaire formulated to investigate degree of acne scarring. The Facial Acne Scar Quality of Life (FASQoL), Dermatology Life Quality Index (DLQI), and Dysmorphic Concern Questionnaire (DCQ) were completed to assess the attitude of these patients toward their scars and the impact of scarring on their HRQOL. Results The mean (standard error) DLQI score for facial acne scars was 6.26 (0.22). Acne scars were considered a ‘very large’ or ‘extremely large’ concern by 19.3% of participants with mild scars as compared to 20.1% and 34.0% of participants with moderate and severe/very severe scars, respectively (P = 0.003). Higher FASQoL scores were associated with increased severity of scarring (P = 0.001). In total, 16.9% of participants had clinical features of dysmorphia (i.e., DCQ > 13). DCQ scores were significantly higher among participants with more severe scarring (mean DCQ score of 8.04 [0.28], 8.40 [0.18], and 10.13 [0.08] among participants with mild, moderate, and severe/very severe acne scars, respectively; P = 0.001). Most commonly reported signs of emotional distress were self-consciousness (68.0%) and worry about scars not going away (74.8%). Conclusions This study highlights the significant psychosocial impact of atrophic acne scars in the form of embarrassment and self-consciousness. Individuals with mild scars also expressed significant impact on quality of life that increased with aggravation of scar severity. Patient-reported outcomes provide an insight into the physical, functional, and psychological impact of acne scarring from the patient’s perspective. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00628-1.

Background: Acne vulgaris and inflammation-associated sequelae are highly prevalent in black and Hispanic populations. In a phase 2 study, a novel polymeric emulsion formulation of tazarotene 0.045% lotion had relatively fewer adverse events than tazarotene 0.1% cream, but with comparable efficacy. The objective was to evaluate tazarotene 0.045% lotion by race and ethnicity in the pivotal trials. Methods: In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1,614). This pooled, post hoc analysis included subsets of participants that self-identified as white (n=1191) or black (n=262) and Hispanic (n=352) or non-Hispanic (n=1262). Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (defined as at least a 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 'clear' or 'almost clear'). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were evaluated. Results: At week 12, tazarotene 0.045% lotion led to significantly greater percent reductions in inflammatory and noninflammatory lesions compared with vehicle in white, Hispanic, and non-Hispanic participants (P

Peer volunteers have been found to be effective in delivering psychosocial interventions when they come from the same culture and share similar experiences as participants. We examined the clinical utility (feasibility and preliminary effectiveness) of a community-based, manualized, peer-delivered group counselling program to address the need for culturally responsive counselling for parents of children with autism in the South Asian community. Sixty-three parents (Mage = 43.7 years, 68% mothers) participated in the program, and reported high stable program satisfaction across sessions. Further, parents reported improved mental health and quality of life following involvement in the program, with changes noted even after the first session. Further research is warranted to assess the efficacy of this kind of parent support intervention.

Rho-associated coiled-coil kinase (ROCK)2 targeting down-regulates autoimmune responses in animal models and patients, however the underlying molecular mechanism is still an enigma. We report that ROCK2 binds phosphorylated-STAT3 and its kinase activity controls the formation of ROCK2/STAT3/JAK2 complex and optimal STAT3 phosphorylation in human CD4+ T cells during T helper 17 (TH17)-skewing. Moreover, chromatin-immunoprecipitation sequencing (ChIP-seq) analysis revealed that, genome-wide, about 70% of ROCK2 and STAT3 peaks overlapped and co-localized to several key genes controlling TH17 and T follicular helper (TFH) cell functions. Specifically, the co-occupancy of ROCK2 and STAT3 on the Irf4 and Bcl6 genes was validated by ChIP-qPCR analysis. Furthermore, the binding of ROCK2 to both the Irf4 and Bcl6 promoters was attenuated by STAT3 silencing as well as by selective ROCK2 inhibitor. Thus, the present study demonstrated previously unidentified evidence that ROCK2-mediated signaling in the cytosol provides a positive feed-forward signal for nuclear ROCK2 to be recruited to the chromatin by STAT3 and potentially regulates TH17/TFH gene transcription.

BACKGROUND School experience is an important part of the life of children with developmental disabilities (DD) and their families. Research suggests that parents of children vary in their level of satisfaction with their child's school, but methodology and results have varied and no consistent reliable measure of school satisfaction exists. This paper presents a new brief measure of school satisfaction along with preliminary information on its psychometric properties. METHOD Parents (n = 185) of children with moderate to severe DD completed a longer questionnaire that included the 9-item GO4KIDDS School Satisfaction Scale. RESULTS The GO4KIDDS School Satisfaction Scale demonstrates high internal consistency reliability (α = 0.93), good item-total correlations, and strong correlations with a single-item rating of school satisfaction. CONCLUSIONS Results support reliability and validity, making the proposed scale valuable for survey research investigating school satisfaction among parents of children with DD.

Background Mental health problems are common among individuals with autism spectrum disorder (ASD), and difficulties with emotion regulation processes may underlie these issues. Cognitive behavior therapy (CBT) is considered an efficacious treatment for anxiety in children with ASD. Additional research is needed to examine the efficacy of a transdiagnostic treatment approach, whereby the same treatment can be applied to multiple emotional problems, beyond solely anxiety. The purpose of the present study was to examine the efficacy of a manualized and individually delivered 10-session, transdiagnostic CBT intervention, aimed at improving emotion regulation and mental health difficulties in children with ASD. Methods Sixty-eight children (M age = 9.75, SD = 1.27) and their parents participated in the study, randomly allocated to either a treatment immediate (n = 35) or waitlist control condition (n = 33) (ISRCTN #67079741). Parent-, child-, and clinician-reported measures of emotion regulation and mental health were administered at baseline, postintervention/postwaitlist, and at 10-week follow-up. Results Children in the treatment immediate condition demonstrated significant improvements on measures of emotion regulation (i.e., emotionality, emotion regulation abilities with social skills) and aspects of psychopathology (i.e., a composite measure of internalizing and externalizing symptoms, adaptive behaviors) compared to those in the waitlist control condition. Treatment gains were maintained at follow-up. Conclusions This study is the first transdiagnostic CBT efficacy trial for children with ASD. Additional investigations are needed to further establish its relative efficacy compared to more traditional models of CBT for children with ASD and other neurodevelopmental conditions.

It is important to understand factors associated with sport participation for youth with intellectual and developmental disabilities (IDD). With a sample of 414 Special Olympics (SO) athletes, this study examined how frequently involved athletes differ from other youth who are less involved in SO. Results showed that frequently involved athletes are older, have more sport-specific parental support, stronger athlete-coach relationships, and more positive SO experiences than other athletes. These factors were predictive of SO involvement, even after controlling for athlete characteristics, including behavior problems and adaptive behavior. Athletes with IDD have the potential to be highly involved in sports when external supports (i.e., coaches and parents) are strong.

Objective Although youth with autism have elevated rates of mental health problems compared to typically developing youth, little is known about the mental health services that they receive. The current study examines predisposing, enabling, and clinical need factors as they relate to mental health service use in youth with autism. Methods The current study surveyed parents of 2337 children and adolescents with autism, compared their access to behavioral management and mental health treatment (MHT), and isolated the correlates of such receipt. Results Children used behavioral management more than adolescents, whereas the opposite was true for MHT. Mental health treatment receipt was associated with caregiver-related and mental health problems in both age groups, with routine health service use in children and with behavioral problems in adolescents. Behavioral management was correlated with caregiver-related services and behavioral problems in both age groups, and with sex and intellectual disability in adolescents. Conclusion Clinical needs and caregiver service use are consistently associated with mental health care across ages, whereas the role of youth characteristics is particularly relevant when considering service use for adolescents.

Background Little is known about sport participation in youth with Autism Spectrum Disorder (ASD). The current study examined sport characteristics (frequency, diversity, positive social experiences [PSE]) for youth with ASD and intellectual disability compared to youth with intellectual disability alone and explored the personal and contextual correlates of involvement. Method Parents (N = 409) completed an online survey, and multiple mediation analyses were used to examine the factors that explained the relationships between sport involvement in youth with ASD and intellectual disability. Results No significant main effects of ASD status were found for frequency or diversity, but youth with intellectual disability alone had higher scores for PSE compared to youth with ASD and intellectual disability. Sociocommunicative abilities, coach relationship and resources mediated the relationship between ASD status and PSE. Conclusions A better understanding of the factors related to sport is essential for allowing families, service providers and policy makers to improve involvement for youth with ASD.

Individuals with autism spectrum disorder (ASD) have many health needs that place demands on the health service sector. This study used administrative data to compare health profiles in young adults 18–24 years of age with ASD to peers with and without other developmental disability. Young adults with ASD were more likely to have almost all the examined clinical health issues and health service use indicators compared to peers without developmental disability. They were more likely to have at least one psychiatric diagnosis, and visit the family physician, pediatrician, psychiatrist, and emergency department for psychiatric reasons, compared to peers with other developmental disability. Planning for the mental health care of transition age adults with ASD is an important priority for health policy.

This study evaluated two community based interventions for parents of adults with autism spectrum disorder and other developmental disabilities. Parents in the mindfulness group reported significant reductions in psychological distress, while parents in the support and information group did not. Reduced levels of distress in the mindfulness group were maintained at 20 weeks follow-up. Mindfulness scores and mindful parenting scores and related constructs (e.g., self-compassion) did not differ between the two groups. Results suggest the psychological components of the mindfulness based group intervention were effective over and above the non-specific effects of group processes and informal support.\ud \ud

Background Adults with Autism Spectrum Disorder (ASD) encounter many difficulties finding and accessing health care services. Despite this, few studies have considered the health service use patterns of adults with ASD without intellectual disability (ID). Objectives The current study examines a diverse range of medical and mental health services and supports, as well as adults' personal experiences accessing and using these services, barriers to service use, and reported unmet service needs. Methods Forty adults (ages 18–61 years) with ASD without ID completed surveys every two months about their health service use for a total of 12–18 months. Bivariate analyses were conducted to understand the individual demographic and clinical factors associated with rate of service use, satisfaction with services, and barriers to health care. Results Results indicated that, beyond a family doctor, the most commonly used services were dentistry, individual counseling, and psychiatry. Individuals who had medical problems experienced significantly more barriers to service use than those who did not, and those who had medical and mental health problems were less satisfied with services. Conclusions Findings highlight the challenges adults with ASD without ID face accessing appropriate, quality services to meet their needs, particularly those with complex medical and mental health issues. Service providers must strive to provide adequate health care to this population who may become distressed if their needs are left unmet.

BACKGROUND Despite the recognised benefits of sport, participation is often reported to be low for youth with intellectual disability (ID). The current study was the first to longitudinally examine sport retention in this population, a critical aspect of ensuring participation. METHODS Study participants were parents/caregivers of athletes with ID involved in community Special Olympics (SO), 11-22 years of age (N = 345). Participants completed an online survey in 2012 that included caregiver demographic and athlete intrapersonal, interpersonal and broader contextual variables. Retention rates for 2019 were determined using the SO provincial registration lists. RESULTS Of the 345 survey participants, 81.7% remained active athletes in 2019. Caregiver demographic and athlete intrapersonal factors were largely unrelated to retention. In contrast, retention was associated with the frequency and number of sports athletes participated in, the perceived psychosocial gains of SO involvement and the environmental supports that were available to facilitate participation; frequency of sport participation was the strongest predictor of remaining a registered athlete. CONCLUSIONS This study has implications for future initiatives aimed at increasing sport retention in a population that struggles to be engaged in sport. Efforts should focus on the athlete experience and sport-specific factors. Coaches and caregivers can foster positive experiences and play an important role in continued sport participation.

Therapeutic alliance is often an important aspect of psychotherapy, though it is rarely examined in clients with autism. This study aims to determine the child pre-treatment variables and treatment outcomes associated with early and late alliance in cognitive behaviour therapy targeting emotion regulation for children with autism. Data were collected from 48 children with autism who participated in a larger randomized-controlled trial. Pre-treatment child characteristics included child, parent, and clinician report of child emotional and behavioural functioning. Primary outcome measures included child and parent-reported emotion regulation. Therapeutic alliance (bond and task-collaboration) was measured using observational coding of early and late therapy sessions. Pre-treatment levels of child-reported emotion inhibition were associated with subsequent early and late bond. Pre-treatment levels of parent and child-reported emotion regulation were related to early and late task-collaboration. Late task-collaboration was also associated with pre-treatment levels of behavioural and emotional symptom severity. Task-collaboration in later sessions predicted improvements in parent-reported emotion regulation from pre- to post-therapy. Future research is needed to further examine the role of task-collaboration as a mechanism of treatment change in therapies for children with autism.

Potent topical corticosteroids (TCSs) are the mainstay of psoriasis treatment. Safety concerns have limited use to 2 to 4 weeks. The objective of our study was to investigate the safety and efficacy of once-daily halobetasol propionate (HP) lotion 0.01% in moderate to severe plaque psoriasis through 2 multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=430). Participants were randomized (2:1) to HP lotion 0.01% or vehicle once daily for 8 weeks, followed by 4 weeks of follow-up. The primary efficacy assessment was treatment success (at least a 2-grade improvement in baseline investigator global assessment [IGA] score and a score of 0 [clear] or 1 [almost clear]). Additional assessments included improvement in psoriasis signs and symptoms, body surface area (BSA), and a composite score of IGA×BSA. Safety and treatment-emergent adverse events (AEs) were evaluated throughout. We found that HP lotion 0.01% demonstrated statistically significant superiority over vehicle as early as week 2 and also was superior in reducing psoriasis signs and symptoms and BSA involvement.

Children with autism spectrum disorder (ASD) often exhibit emotional problems, which can be associated with emotion regulation (ER) difficulties. Parent co-regulation is often associated with child ER and emotional problems, though little work has been done with reference to youth with ASD. This study investigated the association among parent co-regulation, child ER, and internalizing and externalizing problems in 51 parents and school-aged children with ASD. Parent co-regulation strategies and scaffolding were not associated with parent-reported levels of child internalizing problems. Parent scaffolding and child ER predicted externalizing problems, after controlling for child age and IQ. Suggestions for future research on parent involvement in the emotional development of children with ASD are discussed, as well as implications for ER-focused interventions.

Background Many individuals with intellectual disabilities experience challenges to participating in organized sport, despite its known benefits. The aim of this qualitative study was to understand the experiences of participating in sport (Special Olympics) from the perspectives of athletes with intellectual disabilities. Methods Five participants (13-33 years of age) took part in a photo-elicitation project during a 1-month period. Results Our thematic analysis of participant photographs and descriptions revealed the following athlete themes: ‘Connectedness’ and ‘Training in Sport’. Conclusion Photo-elicitation was a useful and important tool in assisting athlete participants to communicate their motivations to participate in sport in ways that using traditional verbal interviewing would not.

// Jian Wang 1 , Peijun He 1 , Matthias Gaida 2 , Shouhui Yang 1 Aaron J. Schetter 3 , Jochen Gaedcke 4 , B. Michael Ghadimi 4 , Thomas Ried 5 , Harris Yfantis 6 , Dong Lee 6 , Jonathan M. Weiss 7 , Jimmy Stauffer 8 , Nader Hanna 9 , H. Richard Alexander 9 , S. Perwez Hussain 1 1 Pancreatic Cancer Unit, Laboratory of Human Carcinogenesis, CCR, NCI, Bethesda, MD, USA 2 Institute of Pathology, University Hospital of Heidelberg, Heidelberg, Germany 3 US Food and Drug Administration, Silver spring, MD, USA 4 Department of General, Visceral and Pediatric Surgery, University Medicine, Gottingen, Germany 5 Genetics Branch, CCR, NCI, Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA 6 Pathology and Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA 7 Cancer and Inflammation Program, CCR, NCI Frederick, MD, USA 8 Laboratory of Cell and Developmental Signaling, NCI Frederick, MD, USA 9 Division of Surgical Oncology, University of Maryland School of Medicine, Baltimore, MD, USA Correspondence to: S. Perwez Hussain, email: hussainp@mail.nih.gov Keywords: NOS2, NO, PDAC, KPC mouse model Received: February 12, 2016 Accepted: June 12, 2016 Published: June 29, 2016 ABSTRACT Pancreatic cancer is one of the most lethal malignancies and is refractory to the available treatments. Pancreatic ductal adenocarcinoma (PDAC) expresses high level of inducible nitric oxide synthase (NOS2), which causes sustained production of nitric oxide (NO). We tested the hypothesis that an aberrantly increased NO-release enhances the development and progression of PDAC. Enhanced NOS2 expression in tumors significantly associated with poor survival in PDAC patients ( N = 107) with validation in independent cohorts. We then genetically targeted NOS2 in an autochthonous mouse model of PDAC to examine the effect of NOS2-deficiency on disease progression and survival. Genetic ablation of NOS2 significantly prolonged survival and reduced tumor severity in LSL-Kras G12D/+ ; LSL-Trp53 R172H/+ ; Pdx-1-Cre (KPC) mice. Primary tumor cells isolated from NOS2-deficient KPC (NKPC) mice showed decreased proliferation and invasiveness as compared to those from KPC mice. Furthermore, NKPC tumors showed reduced expression of pERK, a diminished inactivation of Forkhead box transcription factor O (FOXO3), a tumor suppressor, and a decrease in the expression of oncomir-21, when compared with tumors in KPC mice. Taken together, these findings showed that NOS2 is a predictor of prognosis in early stage, resected PDAC patients, and provide proof-of-principle that targeting NOS2 may have potential therapeutic value in this lethal malignancy.

Background A need exists for topical treatments in managing more severe inflammatory acne. Objectives The objectives of this study were to evaluate the efficacy and safety of adapalene 0.3 %/benzoyl peroxide 2.5 % (0.3 % A/BPO) topical gel in subjects with moderate and severe inflammatory acne. Methods This was a multicenter, randomized, double-blind, parallel-group study. Randomization was stratified by acne severity (50 % moderate and 50 % severe). Subjects received 0.3 % A/BPO, 0.1 % A/BPO (benchmark), or vehicle (comparator) once daily for 12 weeks. Co-primary efficacy endpoints were success rate at week 12 (the percentage of subjects rated ‘clear’ or ‘almost clear’ with at least a 2-grade improvement on Investigator’s Global Assessment [IGA]) and change in inflammatory (IN) and noninflammatory (NIN) lesion counts from baseline to week 12. Secondary efficacy endpoints were percent changes in IN and NIN lesion counts. Safety endpoints were incidence of adverse events (AEs) and local tolerability signs/symptoms. Results A total of 503 subjects were randomized: 217, 217, and 69 subjects in the 0.3 % A/BPO, 0.1 % A/BPO, and vehicle groups, respectively. For success rate (subjects rated ‘clear’ or ‘almost clear’ with ≥2-grade improvement in IGA), 0.3 % A/BPO was superior to vehicle, with a treatment difference of 22.7 % (33.7 vs. 11.0 %; 95 % confidence interval [CI] 12.8–32.6, p

Background Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. Objectives Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne. Methods Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator's Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. Results In both studies, at week 12 the facial success rates according to the Investigator's Global Assessment and truncal Physician's Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P Limitations Adjunctive topical or systemic treatments were not studied. Conclusion These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne.

FMX101 4% is a topical minocycline foam for the treatment of moderate-to-severe acne.Evaluate the efficacy and safety of FMX101 4% in treating moderate-to-severe acne vulgaris.Two identical phase 3 studies were conducted. Subjects were randomized 2:1 to once-daily FMX101 4% or foam vehicle for 12 weeks. The coprimary end points were the change in inflammatory lesion count from baseline and the rate of treatment success according to the Investigator's Global Assessment (a score of 0 or 1 for clear or almost clear, with a ≥2-grade improvement) at week 12.A total of 961 subjects were enrolled (study 04, N = 466; study 05, N = 495). Compared with vehicle, FMX101 4% demonstrated a significantly greater reduction in inflammatory lesions in both studies (P .05) and a greater rate of treatment success in study 05 according to the Investigator's Global Assessment (P .05). Pooled analyses of the 2 studies demonstrated statistical significance for both coprimary end points (all P .05). Noninflammatory lesion count was also significantly reduced with FMX101 4% versus with vehicle in both studies. FMX101 4% was generally safe and well tolerated. Skin-related adverse events were reported in less than 1% of subjects treated with FMX101 4%.Longer-term efficacy and safety outcomes are needed (ongoing).FMX101 4% topical minocycline foam significantly reduced both inflammatory and noninflammatory lesions and improved Investigator's Global Assessment scores in patients with moderate-to-severe acne.

This study aimed to describe patterns of emergency department use and police interactions, as well as satisfaction with emergency services of 40 adults with autism spectrum disorder without intellectual disability over 12–18 months. Approximately 42.5% of the sample reported visiting the emergency department and 32.5% reported interactions with police during the study period. Presenting concerns for emergency department use and police interactions varied widely, highlighting the heterogeneous needs of this population. On average, participants reported being dissatisfied with care received in the emergency department while police interactions were rated relatively more favourably.

Children with autism spectrum disorder (ASD) often present with comorbid psychopathology including problems with emotion regulation. The goal of the present research was to investigate the feasibility of a multicomponent manualized cognitive behavior therapy treatment program for improving emotion regulation in youth with ASD 8-12 years of age. Thirteen males and their parents participated in the intervention, reporting high satisfaction with the activities and program overall, and attending all sessions. Preliminary outcomes regarding emotion regulation and psychopathology, and feasibility of the intervention, are summarized and discussed.

Psychotropic medications are frequently used to treat mental health and behavioral issues in adolescents and adults with an autism spectrum disorder (ASD). Although parents of individuals with ASD frequently take on medication management for their child, there is limited literature on parent perspectives of their child's medication use or their views about the healthcare services they receive, particularly in adulthood. The current study examined and compared parents of adolescents and of young adults with ASD regarding their child's psychotropic medication use and their views about healthcare services.One hundred parents of adolescents and young adults with ASD (ages 12-30 years) completed an online survey about their experience with their child's healthcare services and medication use.Parents of young adults were less likely to use nonpharmacological services before using a psychotropic medication than were parents of adolescents. Parents of young adults were also less likely to believe that their prescribing healthcare provider had adequate expertise in ASD, and were less satisfied with how their prescriber monitored their child's medication use.Findings highlight the need to build capacity among healthcare providers supporting individuals with ASD as they transition into adulthood. There is also a need for improved medication monitoring and increased awareness of the different mental health challenges that individuals with ASD encounter as they age.

Although electronic technology currently plays an integral role for most youth, there are growing concerns of its excessive and compulsive use. This study documents patterns and impact of electronics use in individuals with autism spectrum disorder compared to typically developing peers. Participants included 172 parents of typically developing individuals and 139 parents of individuals with an autism spectrum disorder diagnosis, ranging in age from 6 to 21 years. Parents completed an online survey of demographics and the frequency, duration, and problematic patterns of electronics use in their youth and young adults. Individuals with autism spectrum disorder were reported to use certain electronics more often in the last month and on an average day, and had greater compulsive Internet and video game use than individuals without autism spectrum disorder. Across both samples, males used video games more often than females. Compared to parents of individuals without autism spectrum disorder, parents of individuals with autism spectrum disorder were significantly more likely to report that electronics use was currently having a negative impact. The implications of problematic electronics use for individuals with autism spectrum disorder are discussed.

Children with autism spectrum disorder (ASD) benefit from parent involvement in their therapy, and there is evidence that this involvement may improve parent functioning as well. We examined changes in parent mental health, parenting, and expressed emotion, following participation in a randomized controlled trial of cognitive behavior therapy for 57 children with ASD. Post-intervention, improvements occurred in the treatment group in parent depression and emotion regulation, compared to waitlisted parents. Treatment effects also occurred across all parents in depression, emotion regulation, perceptions of their children and mindful parenting. Though preliminary, these results have implications for intervention development and evaluation by focusing on parent outcomes in child treatment.

pBackground: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.05%) is approved for topical treatment of AK in a single contiguous area of ~25 cm2./ppObjective: The study sought to determine the maximum tolerated dose (MTD), efficacy, and tolerability of IngMeb applied to AK on a contiguous area less than equal to 250 cm2./ppMethods: Part 1 determined the MTD of IngMeb at 7 concentrations for 2 or 3 days. Part 2 assessed efficacy and tolerability at the MTD and one dose lower for 2 or 3 days vs vehicle./ppResults: Four dosing regimens with an acceptable benefit-to-risk ratio were identified: 0.018% and 0.027% once daily for 2 or 3 days. Complete clearance at 8 weeks was achieved by 21.3% to 39.1% of IngMeb-treated patients vs 0% to 3.2% treated with vehicle. Composite local skin response scores peaked on the day after the last application, rapidly declined, and were near baseline at 2 weeks. Adverse events were predominantly mild or moderate./ppLimitations: The study evaluated a limited number of doses in a population of only white patients./ppConclusion: IngMeb gel was effective and well tolerated as field treatment of AK on the full face, full scalp, and up to 250 cm2 on the chest./ppemJ Drugs Dermatol. 2017;16(5):438-444./em/p.

This study aimed to describe police interactions, satisfaction with police engagement, as well as examine correlates of police involvement among 284 adolescents and adults with autism spectrum disorder (ASD) followed over a 12- to 18-month period. Approximately 16% of individuals were reported to have some form of police involvement during the study period. Aggressive behaviors were the primary concern necessitating police involvement. Individuals with police involvement were more likely to be older, have a history of aggression, live outside the family home, and have parents with higher rates of caregiver strain and financial difficulty at baseline. Most parents reported being satisfied to very satisfied with their children's police encounters. Areas for future research are discussed in relation to prevention planning.

Parents of children diagnosed with autism spectrum disorder often report higher levels of depression, anxiety, and mental health–related issues. The combination of stressors and family adjustment difficulties can cause distress which may develop into a crisis. Understanding crisis in the family is important to mental health practice since it can serve as a guide in delivering service to at-risk families. This study investigated the subjective experience of crisis in 155 mothers of children diagnosed with autism spectrum disorder. Thematic analysis revealed that crisis is characterized by factors influencing four major areas: demands, internal capabilities, external resources, and subjective appraisal. Understanding what crisis means to families of individuals with autism spectrum disorder can help inform effective preventative and crisis services.

Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin. We observed significant reductions of IL-17 and IL-23, but not IL-6 and TNF-α, whereas IL-10 levels were increased in peripheral blood of clinical responders after 12 wk of treatment with KD025. Collectively, these data demonstrate that an orally available selective ROCK2 inhibitor downregulates the Th17-driven autoimmune response and improved clinical symptoms in psoriatic patients via a defined molecular mechanism that involves concurrent modulation of cytokines without deleterious impact on the rest of the immune system.

Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cellswhich provide help necessary to generate antibody-producing B cells in normal and autoimmune conditionsWe found that targeting ROCK2 in normal human T cells or peripheral blood mononuclear cells (PBMCs) from patients with active systemic lupus erythematosus (SLE) decreased the number and function of Tfh cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity concomitantly decreased the abundance of the transcriptional regulator Bcl6 and increased that of Blimp1 by xxx concurrent regulation of the binding of signal transducer and activator of transcription 3 (STAT3) and STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively. In the MRL/lpr murine model of SLE, oral administration of the selective ROCK2 inhibitor KD025 resulted in a two-fold reduction in the numbers of Tfh cells and antibody-producing plasma cells in the spleen, as well as a decrease in the size of splenic germinal centers, sites of interaction between TFH cells and B cells. KD025-treated mice showed a substantial improvement in both histological and clinical scores compared to those of untreated mice, and had reduced amounts of Bcl6 and phosphorylated STAT3, as well as increased STAT5 phosphorylation. Together, these data suggest that ROCK2 signaling plays a critical role in controlling the development of Tfh cells induced by autoimmune conditions through reciprocal regulation of STAT3 and STAT5 activation.

Treatment of acne vulgaris (acne) with dapsone gel, 5% requires twice-daily dosing, and some patients may not adhere to this regimen.br /The objective of this study was to assess the efficacy and safety of a new, once-daily formulation of dapsone gel, 7.5%, with a 50% higher dapsone concentration, versus vehicle over 12 weeks in patients with acne.br /This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients with moderate acne aged 12 years and older with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized to receive topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.br /The intent-to-treat population comprised 2102 patients, 1044 in the dapsone gel, 7.5% group and 1058 in the vehicle group. At week 12, 29.9% of patients in the dapsone gel, 7.5% group and 21.2% in the vehicle group (P.001) had GAAS success. Mean inflammatory lesions decreased by 55.5% and 49.0%, noninflammatory lesions decreased by 44.4% and 38.4%, and total lesions decreased by 48.7% and 42.4% in the dapsone gel, 7.5% and vehicle groups (all P.001), respectively, at week 12. The incidence of adverse events was similar in the dapsone gel, 7.5% (19.1%) and vehicle (20.6%) groups. Most events in both groups were mild or moderate in severity. Most patients receiving dapsone gel, 7.5% and vehicle had a severity rating of "none" for stinging/burning, dryness, scaling, and erythema scales at all time points.br /Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne.br /br /emJ Drugs Dermatol/em. 2016;15(5):553-561.

A novel formulation of 0.05% betamethasone dipropionate in an emollient spray vehicle (DFD-01) was developed to deliver steroid to the skin layers most affected by psoriasis.To compare the efficacy and safety of DFD-01 to its vehicle for the treatment of moderate plaque psoriasis over 4 weeks.Two Phase 3 trials enrolled adults with moderate psoriasis (Investigator Global Assessment [IGA]=3; 10-20% body surface area [BSA]) and randomized them 2:1 to DFD-01 or Vehicle. Products were applied twice daily to affected areas for 28 days. Treatment success was defined as an IGA=0 or 1 and ≥ 2-grade improvement from baseline. Primary endpoint was the proportion of subjects achieving treatment success at day 15.Moderate psoriasis subjects were enrolled in Study 1 (174 DFD-01; 87 Vehicle) and Study 2 (182 DFD-01; 95 Vehicle). Mean BSA was 13-14%. Treatment success was achieved in significantly more subjects using DFD-01 than Vehicle at day 15 in both Study 1 (P0.001) and Study 2 (P=0.002), and at day 29 (both studies P0.001). Treatment success with DFD-01 was significant at day 8 in Study 1 (P=0.003) but not in Study 2 (P=0.156). Erythema, scaling, and plaque elevation scores of target lesions were significantly reduced as early as day 4 with DFD-01. Adverse events were similar between groups, with no increase between 2 and 4 weeks.These studies demonstrate DFD-01's excellent efficacy and safety for the treatment of extensive psoriasis (10-20% BSA). DFD-01 achieved treatment success in significantly more subjects than Vehicle after 2 and 4 weeks of treatment, and showed early onset of action with improved signs of erythema, scaling and elevation of target lesions after 4 days of treatment. This medium potency formulation provides a safe and effective choice for topical steroid treatment of psoriasis.

MIF is a proinflammatory cytokine and is implicated in cancer. A higher MIF level is found in many human cancer and cancer-prone inflammatory diseases, including chronic pancreatitis and pancreatic cancer. We tested the hypothesis that MIF contributes to pancreatic cancer aggressiveness and predicts disease outcome in resected cases. Consistent with our hypothesis we found that an elevated MIF mRNA expression in tumors was significantly associated with poor outcome in resected cases. Multivariate Cox-regression analysis further showed that MIF is independently associated with patients' survival (HR = 2.26, 95% CI = 1.17-4.37, p = 0.015). Mechanistic analyses revealed that MIF overexpression decreased E-cadherin and increased vimentin mRNA and protein levels in pancreatic cancer cell lines, consistent with the features of epithelial-to-mesenchymal transition (EMT). Furthermore, MIF-overexpression significantly increased ZEB1/2 and decreased miR-200b expression, while shRNA-mediated inhibition of MIF increased E-cadherin and miR-200b expression, and reduced the expression of ZEB1/2 in Panc1 cells. Re-expression of miR-200b in MIF overexpressing cells restored the epithelial characteristics, as indicated by an increase in E-cadherin and decrease in ZEB1/2 and vimentin expression. A reduced sensitivity to the chemotherapeutic drug, gemcitabine, occurred in MIF-overexpressing cells. Indicative of an increased malignant potential, MIF over-expressing cells showed significant increase in their invasion ability in vitro, and tumor growth and metastasis in an orthotopic xenograft mouse model. These results support a role of MIF in disease aggressiveness, indicating its potential usefulness as a candidate target for designing improved treatment in pancreatic cancer.

Objective We sought to evaluate efficacy, safety, and tolerability of a combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% (clindamycin-BPO 2.5%) aqueous gel in moderate to severe acne vulgaris. Methods A total of 2813 patients, aged 12 years or older, were randomized to receive clindamycin-BPO 2.5%, individual active ingredients, or vehicle in two identical, double-blind, controlled 12-week, 4-arm studies evaluating safety and efficacy (inflammatory and noninflammatory lesion counts) using Evaluator Global Severity Score and subject self-assessment. Results Clindamycin-BPO 2.5% demonstrated statistical superiority to individual active ingredients and vehicle in reducing both inflammatory and noninflammatory lesions and acne severity. Visibly greater improvement was observed by patients with clindamycin-BPO 2.5% as early as week 2. No substantive differences were seen in cutaneous tolerability among treatment groups and less than 1% of patients discontinued treatment because of adverse events. Limitations Data from controlled studies may differ from clinical practice. Conclusions Clindamycin-BPO 2.5% provides statistically significant greater efficacy than individual active ingredients and vehicle with a highly favorable safety and tolerability profile.

The Pediatric Quality of Life Inventory (PedsQL) measures health-related quality of life, a growing area of research, particularly among individuals with disabilities. This research is necessary to fully understand the varied needs of the population and, ultimately, ensure that those needs are being met. The current study assessed the reliability and validity of the PedsQL in individuals with intellectual and developmental disabilities, including individuals with autism spectrum disorder. Participants included 359 caregivers of children, youth, and young adults with IDD. Caregivers completed the PedsQL 4.0 Generic Core Scales questions regarding the individual's physical health and the Strengths and Difficulties Questionnaire. The PedsQL achieved excellent reliability across scales, and distinguished healthy individuals from those with chronic health conditions, as well as individuals with ASD from those without. Factor analysis confirmed a 5-factor model, with moderate to high criterion validity. The PedsQL shows sound psychometric properties and may be a useful tool to measure psychosocial functioning in this population.

Many parents of adolescents and adults with autism spectrum disorder experience difficulty accessing appropriate services for their children, and may report low levels of parent self-efficacy. In an effort to identify the factors that contribute to the difficulties these families face, this study examined the role of demographic, systemic, and clinical need variables as they relate to parents’ experience of self-efficacy. Participants included 324 parents of individuals with autism spectrum disorder, 12–25 years of age. Results suggest that parent self-efficacy is related to a number of variables and not simply a child’s clinical situation, including child age, parent immigrant status, barriers to service access, and caregiver burden. Given the crucial role that parents often play in the lives of individuals with autism spectrum disorder across the lifespan, it is important that service providers support the efforts of parents who provide and access care for their children.

Most research on mental health in individuals with autism spectrum disorder (ASD) and intellectual disability (ID) has focused on deficits. We examined individual (i.e., sociocommunicative skills, adaptive behavior, functional cognitive skills) and contextual (i.e., home, school, and community participation) correlates of thriving in 330 youth with ID and ASD compared to youth with ID only, 11–22 years of age (M = 16.74, SD = 2.95). Youth with ASD and ID were reported to thrive less than peers with ID only. Group differences in sociocommunicative ability and school participation mediated the relationship between ASD and less thriving. Research is needed to further elucidate a developmental-contextual framework that can inform interventions to promote mental health and wellness in individuals with ASD and ID.

Using a nonviral, electroporation-based gene transfection approach, we demonstrate the efficient and consistent transfection of two poorly immunogenic tumor cell lines: B16F10 melanoma and renal carcinoma (RENCA). Three genes, IL-12, angiostatin (AS), and an endostatin:angiostatin fusion protein (ES:AS) were subcloned into a DNA plasmid containing EBNA1-OriP, which was then transfected into B16F10 and RENCA cells. Significant levels of protein were secreted into the culture supernatants of transfected cells in vitro. Transfected tumor cells were injected subcutaneously into mice. All the three transgenes were capable of significantly delaying and reducing the formation of primary B16F10 and RENCA tumors, as well as B16F10 lung metastases. By day 11 post-injection, all control mice that received either mock-transfected or empty vector DNA-transfected B16F10 tumor cells had developed large primary tumors. In contrast, mice that received IL-12-transfected B16F10 cells did not develop appreciable tumors until day 17, and these were significantly smaller than controls. Similar results were observed for the RENCA model, in which only one of the IL-12 mice had developed tumors out to day 31. Expression of AS or ES:AS also significantly delayed and reduced primary tumors. Overall, ES:AS was more effective than AS alone. Furthermore, 25% of the AS mice and 33% of the ES:AS mice remained tumor-free at day 17, by which point all control mice had significant tumors. Mouse survival rates also correlated with the extent of tumor burden. Importantly, no lung metastases were detected in the lungs of mice that had received either AS or ES:AS-transfected B16F10 tumor cells and significantly fewer metastases were found in the IL-12 group. The consistency of our transfection results highlight the feasibility of directly electroporating tumor cells as a means to screen, identify, and validate in vivo potentially novel antiangiogenic and/or antineoplastic genes.

The current study examined the relations among components of a physical activity program, Special Olympics (SO), and the self-concepts (i.e., perceived physical competence, social acceptance, and general self-worth) and adaptive behaviors of individuals with developmental disabilities. This research can assist in the development of theoretical models of how physical activity programs can be implemented to effect psychological change. Participants consisted of a randomly selected group of 97 individuals with developmental disabilities, between 9 and 43 years of age, and their parents. Participants' self-concepts and adaptive behaviors were measured both by direct interview and parental report. Examined program components consisted of the length of time affiliated to the organization, number of competitions attended, of hours spent in training, of sports, and of medals obtained. Multiple regression analyses suggest relations between specific components of SO and participants' self-concepts and adaptive behaviors. These relations highlight the importance of competition and sport for individuals with developmental disabilities.

Background Parents often play a lifelong role in supporting their sons and daughters with intellectual and/or developmental disabilities (IDD). There is a need to better understand parent resources, particularly when the individual with IDD has behaviour problems, as the latter has consistently been linked to parental burden. Methods The current study aimed to investigate the relationship between the behaviour support needs of 212 adults with IDD and parental burden, and whether perceived helpfulness of informal supports moderated this relationship. The helpfulness of individual sources of informal support was also explored. Results Informal support was negatively related to burden, although it did not act as a moderator. Individual sources varied in terms of how they were related to burden, but none acted as moderators. Conclusions Although informal social support appears to be important to parents and may help alleviate burden, it does not appear to act as a moderator as anticipated.

Objectives To determine predictors of emergency department (ED) visits in a cohort of adolescents and adults with autism spectrum disorder (ASD). Design Prospective cohort study. Setting Community-based study from Ontario, Canada. Participants Parents reported on their adult sons and daughters with ASD living in the community (n=284). Main outcome measures ED visits for any reason, ED visits for medical reasons and ED visits for psychiatric reasons over 1 year. Results Among individuals with ASD, those with ED visits for any reason were reported to have greater family distress at baseline (p

Background Accurate measurement of adaptive behaviour is important in both clinical and research contexts. While several good clinical measures exist, as well as brief research measures for adults with intellectual disability, there is need for a brief and efficient measure for research with children and youth. We present preliminary psychometric properties of a new scale we developed for such purposes, the GO4KIDDS Brief Adaptive Behaviour Scale. Materials and Methods A large sample (n = 432) of parents of youth (aged 3–20) with intellectual disability and/or ASD completed an online survey that included the new scale. A subsample of these parents (n = 204) also completed the Scales of Independent Behavior-Revised Short Form (Scales of Independent Behavior—Revised Comprehensive Manual, 1996 and Riverside Publishing). Results The new scale has good internal consistency and correlates strongly with the Scales of Independent Behavior, thus supporting its reliability and validity. Conclusions Although we do not recommend its use for clinical purposes, the GO4KIDDS Brief Adaptive Behaviour Scale may be useful for survey research with parents of children and youth with developmental disabilities.

This study examined the child, parent, and service factors associated with polypharmacy in adolescents and young adults with autism spectrum disorders (ASD).As part of an online survey examining health service utilization patterns among individuals with ASD, parents provided demographic and clinical information pertaining to their child. This included information on current medication use, as well as information on clinical services received, clinical history, and parent well-being. Analyses examined the bivariate association between individual child, parent, and service variables and polypharmacy. Variables significantly associated with polypharmacy were included in a multiple variable logistic regression.Of the 363 participants sampled, ∼25% were receiving two or more psychotropic drugs concurrently. The patient's psychiatric comorbidity, history of hurting others, therapy use, and parent burden were predictors of polypharmacy.Adolescents and young adults with ASD are a highly medicated population with multiple factors associated with psychotropic polypharmacy. Although there may be circumstances in which polypharmacy is necessary, a richer understanding of what predicts polypharmacy may lead to targeted interventions to better support these individuals and their families. Findings also highlight the need to support families of children with ASD prescribed multiple psychotropic medications.