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Understanding the role of therapeutic process factors in treatment change may prove useful for discerning why some autistic youth benefit from psychosocial interventions that target emotional and psychological aspects of mental health, while others do not. The aim of the current study was to synthesize what is currently known about therapeutic process factors in mental health treatment of emotional and psychological challenges for autistic youth, regarding how process factors have been measured in past research, and the relation between process factors and treatment outcome. A systematic review of the literature was conducted to narratively synthesize all articles published up until June 2021. Methodological quality of included studies was appraised. Twenty-five studies met inclusion criteria. Process factors assessed across studies included relational factors; treatment expectations, readiness, and satisfaction; and treatment engagement from youth and their parents. Process-outcome associations were reported for a limited number of constructs. There is a limited, albeit growing, body of high-quality research evaluating the role of process factors in the treatment of mental health issues for autistic youth. Future research should continue to examine process factors in relation to treatment outcome, and validate measures to accurately capture process-related constructs in mental health treatment for this population. Greater understanding of therapy processes can lead to developing evidence-informed strategies that clinicians can implement to promote positive expectations, relationships, and engagement.

This pilot study examined associations between transdiagnostic symptoms and parent-perceived parent-child relationship quality in treatment-seeking families of children with neurodevelopmental disabilities, and interactions among clinical symptoms and cognitive functioning. Sixty-three children between 8 to 13 years of age and their caregivers were assessed at baseline while seeking cognitive behaviour therapy for emotion regulation and mental health difficulties. Diagnoses included autism, ADHD, cerebral palsy, and learning disability, with 52% of children having multiple diagnoses. Parent-perceived parent-child relationship quality was assessed by the Positive Affect Index, autism symptoms (e.g., social communication, repetitive behaviours) by the Social Responsiveness Scale, Second Edition, mental health (i.e., internalizing problems, externalizing problems, behavioural symptoms) by the Behaviour Assessment Scale for Children, Third Edition, and IQ by the Weschler Abbreviated Scale of Intelligence, Second Edition. Results revealed that higher IQ scores and greater social communication challenges, externalizing problems, and behavioural symptoms, were associated with lower parent-child relationship quality. Interaction effects were found between IQ and social communication challenges, reflecting significantly stronger relationships between social communication challenges and lower parent-child relationship quality in the context of higher IQ. Understanding the interactions between cognitive functioning and social communication challenges can help to inform individualized supports, and advocate for a transdiagnostic approach to intervention.

Supplementary Figure 7 - PDF file 111K, Characterization of myeloid cells in lung, tumor, spleen, and lymph nodes

Supplementary Figure 1 - PDF file 183K, Overproduction of immature myeloid cells in both tumor bearing mice and cancer patients, flow cytometry analysis and sorting

Supplementary Figure 4 - PDF file 129K, Validation of over expression of TGFbeta1, IL-4, IL10, as well as Arginase1 and iNOS in Tgfbr2

Supplementary Figure 3 - PDF file 76K, IFN-gamma production by T cells and its effect on tumor growth in Tgfbr2MyeKOand Tgfbr2flox/flox control mice

Supplementary Figure 8 - PDF file 84K, Immune cell profiling and IFN-gamma production in CD8 T cells in tumor tissues between Tgfbr2flox/flox and Tgfbr2MyeKO mice bearing 4T1 tumors

Supplementary Figure 9 - PDF file 150K, Gating strategy, sorting efficiency, and TbetaRII expression in myeloid cell subsets

TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2MyeKO) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2MyeKO bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-β1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-γ production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2MyeKO mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-β receptor II expression. Our studies show that myeloid-specific TGF-β signaling is an essential component of the metastasis-promoting puzzle of TGF-β. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.Significance: Our study identifies myeloid-specific TGF-β signaling as a critical mediator in tumor metastasis, distinct from the tumor-suppressive effect of TGF-β signaling in epithelial cells, fibroblasts, and T cells. We further provide mechanistic insight into host antitumor immunity and suggest a cell type–specific cancer-targeting strategy. Cancer Discov; 3(8); 936–51. ©2013 AACR.See related commentary by Souza-Fonseca-Guimaraes and Smyth, p. 846This article is highlighted in the In This Issue feature, p. 826

Supplementary Figure 5 - PDF file 382K, Analysis of percentage or number in B cells, T cells, or myeloid cell subsets in the lungs between Tgfbr2MyeKO and control littermates under normal or tumor conditions

Supplementary Figure Legends, Supplementary Tables 1-2 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 2 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Table 1. Th1 vs. Th2 Cytokine Trend. Supplementary Table 2. Effect of L-NAME on Radiation-induced Cytokine Expression.

Supplementary Figure 3 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 4 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 1 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 1 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 4 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 5 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 3 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 6 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 5 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 2 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Background Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients. Objectives To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden. Methods The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting "agree" or "strongly agree." All voting was electronic and blinded. Results Key management domains, consisting of distinct considerations, points to discuss with patients, and "pivot points" were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients. Limitations Recommendations are based on expert opinion, which could potentially differ from patients' perspectives. Regional variations in health care systems may not have been captured. Conclusions The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey.

Cognitive behavior therapy (CBT) is an effective treatment for many autistic children experiencing mental health problems, and parents are particularly involved in their psychotherapy. This study presents a conceptual framework of successful parent involvement in CBT for autistic children. Seventeen therapists (94% female) and 11 mothers were interviewed about their involvement in a CBT program for autistic children ages 8-13 years. The conceptual framework depicts how parent involvement varies depending on child, parent, and environmental factors. Parents’ contributions to therapy were grouped into five main roles. Parents’ beliefs and attitudes toward therapy also influenced their involvement. This is the first study to empirically investigate how parents of autistic children contribute to the therapeutic process in CBT.

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.

Objectives Adolescents with autism often experience comorbid internalizing disorders such as anxiety disorders or depression but the available evidence-based treatments to support the mental health of adolescents with autism are limited. The aim of this study was to investigate if and how MYmind, a mindfulness-based program (MBP) for youth with autism, could benefit adolescents with comorbid internalizing disorder(s). Methods A person-centered approach with a multiple baseline design was used to investigate the effects of MYmind. Five adolescents with autism and an internalizing disorder took part in the 9-week MYmind program. The adolescents and their parents completed a daily questionnaire on their personal goals during a baseline phase, the intervention, a 2-month follow-up phase, and a 1-year follow-up phase. We analyzed the effects on their personal goals using visual inspection and statistical analysis for single-case designs. Also, we investigated potential processes of change by analyzing how changes were related over time. Results Findings indicated that most, but not all, adolescents benefitted from the MBP. Four out of five adolescents showed medium-sized improvement in some of their personal goals. However, one adolescent reported a deterioration during the intervention and 2-month follow-up phase. Decreased worry preceded behavioral improvements in two adolescents, whereas other potential mechanisms of change showed inconclusive results. Conclusion The findings indicated that most of the adolescents with autism and a comorbid internalizing disorder partially benefitted from the MBP.

Caregivers and families of autistic people have experienced stress and increase in demands due to the COVID‐19 pandemic that may have long‐term negative consequences for both their own and their children's mental health. A scoping review was conducted to identify pandemic related demands experienced by caregivers and families of autistic children and youth. The review also consolidated information on coping strategies and parenting‐related guidelines that have emerged to help parents meet these demands. Search strategies were approved by a research librarian and were conducted in peer‐reviewed and gray literature databases between May 2020 and February 2021. Additional resources were solicited through author networks and social media. All articles were published between December 2019 and February 2021. Article summaries were charted, and a thematic analysis was conducted with confirmation of findings with our knowledge users. Twenty‐three published articles and 14 pieces of gray literature were included in the review. The majority of articles characterized and highlighted the increase in demands on caregivers of autistic children and youth during the pandemic globally. Both quantitative and qualitative studies suggest that parents have experienced an increase in stress and mental health‐related symptoms during lockdown measures. Findings suggest that families are employing coping strategies, but there no evidence‐based supports were identified. The review highlighted the potential long‐term impact of prolonged exposure to increasing demands on the mental health and wellbeing of caregivers and families of autistic people, and pointed to a need for the rapid development and evaluation of flexible and timely support programs. Lay Summary Caregivers and families of autistic children and youth have faced increased demands due to pandemic‐related lockdown measures. We reviewed the literature to outline sources of stress, links to their influence on caregiver mental health, and if support programs have emerged to help them. Our findings suggest a number of demands have increased caregivers' risk to mental health challenges, and their potential impact on family wellbeing. Ongoing development of evidence‐based supports of all families of autistic children and youth are needed.

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III–VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae.

Autistic youth have an increased risk of mental health problems. Despite the efficacy of various psychotherapeutic approaches for autistic youth, they often do not receive these interventions. Research is needed to identify patterns of effective treatment for autistic youth and whether they differ from those used for youth with other neurodevelopmental conditions (e.g., attention-deficit hyperactivity disorder; ADHD). We compared clinicians' (N = 557) knowledge, confidence and practices when treating autistic youth and youth with ADHD. Although ratings were moderately high overall and similar interventions were used for both groups, clinicians were significantly less knowledgeable and confident when supporting autistic clients compared to clients with ADHD. Thus, improving clinician perspectives may help facilitate treatment for autistic youth with mental health problems.

Background The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes. Objective To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance. Methods The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting "agree" or "strongly agree." All voting was electronic and blinded. Results The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae. Limitations The recommendations are based on expert opinion and made in the absence of high-quality evidence. Conclusions The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management.

Distancing requirements due to the pandemic have halted many in-person therapeutic programs, including cognitive behavior therapy (CBT), increasing the likelihood that autistic children with mental...

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.

Early motor skill interventions have been shown to improve the motor skill proficiency of children with autism spectrum disorder; however, little is known about the secondary effects associated with these types of interventions (e.g., influence on behavior, social skills, family dynamics). The purpose of this qualitative study was to (a) investigate parents’ perceptions of the child-level benefits associated with a fundamental motor skill intervention for their 4-year-olds with autism spectrum disorder and (b) explore how child-level benefits influenced the family unit. Eight parents (N = 8) were interviewed (semistructured) about their experiences with the intervention for their child(ren); the study was grounded in phenomenology. Five main child-level benefits emerged, including improvements with (a) motor skills, (b) social skills, (c) listening skills, (d) turn-taking skills, and (e) transition skills. The child-level benefits then extended to family members in a number of ways (e.g., more positive sibling interactions). These findings highlight several important secondary effects that should be investigated in future research.

Autistic children and adolescents are more likely than non-autistic youth to experience mental health problems, such as anxiety or depression, but less likely to receive psychotherapy to address these concerns. Recent research indicates that clinician factors, such as knowledge, attitudes, confidence and beliefs, can impact their decisions to provide care, though this work has primarily focused on adults or within the context of one kind of treatment (cognitive behaviour therapy). The current study examined psychological predictors (e.g. attitudes and confidence) of clinicians’ intention to deliver psychotherapy to autistic youth and those with attention-deficit hyperactivity disorder. Participants included 611 clinicians across publicly funded agencies in Ontario, Canada. Multiple mediation analyses revealed that clinician knowledge on mental health-related topics (e.g. core symptoms, developing treatment plans and identifying progress towards treatment goals) was associated with intention to treat autistic clients or clients with attention-deficit hyperactivity disorder, and normative pressures and attitudes partially mediated this association. Clinicians felt less likely to treat autistic clients than clients with attention-deficit hyperactivity disorder, partly because of differences in attitudes, normative pressures and knowledge. This research suggests that targeted training around autism and mental health care may be a useful initiative for agency staff. Lay abstract Autistic children and youth often experience mental health problems, such as anxiety, depression and behavioural challenges. Although there are therapy programmes that have been found helpful in reducing these issues, such as cognitive behaviour therapy, autistic children often struggle to receive adequate mental health care. Clinicians’ knowledge, attitudes, confidence and beliefs about treating mental health problems in autistic people may be related to their choices in providing psychotherapy. Across Ontario, Canada, 611 mental health clinicians, working in publicly funded agencies, completed an online survey about their experiences and opinions on delivering therapy for autistic clients compared to those with attention-deficit hyperactivity disorder. Clinician knowledge was associated with their intention to treat autistic clients or clients with attention-deficit hyperactivity disorder, partly because of their attitudes and the social pressures or values they felt. Clinicians reported feeling less intent on providing therapy to autistic youth compared to youth with attention-deficit hyperactivity disorder because of differences in their attitudes, social pressures and knowledge. This research can inform the training and educational initiatives for mental health practitioners.