Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study.

Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.

Caring for children with mental health or developmental and behavioural disorders: Perspectives of family health teams on roles and barriers to care.

OBJECTIVE: To inform a shared care model between developmental and behavioural (DB) and mental health specialists and primary care physicians by having members of primary care family health teams (FHTs) report on strengths of and barriers to providing care for children with DB disorders and mental health concerns. DESIGN: Qualitative study using semistructured focus groups. SETTING: Academic and community-based FHTs in Toronto, Ont. PARTICIPANTS: Primary care physicians, nurses, allied health professionals, and family medicine trainees within the participating FHTs. METHODS: Nine focus groups were conducted with FHT members, and transcripts were analyzed for key themes using an inductive thematic analysis approach. MAIN FINDINGS: Eighty-four participants across 9 sites were interviewed. Six sites were academically affiliated and 3 were community based. Participants described their roles in the care of children with DB disorders as primarily "referral agent" but also as "long-term supporter" and "health care coordinator." Family health team members expressed the desire to "learn" and "do more" for these children but noted numerous barriers to providing care, captured in 4 overarching themes: limited training beyond how to screen, lack of service knowledge, limited time and communication, and cumbersome access to mental health and dual diagnosis services. CONCLUSION: Primary care physicians are in the unique position of being able to provide longitudinal care for children with DB and mental health disorders. However, they perceive barriers to providing care that can affect access to services, service quality, and health outcomes for these children and their families. The health system might benefit from addressing these barriers by providing more training for primary care physicians in the longitudinal care of children with mental health and DB disorders, and by improving communication between FHTs and DB and mental health specialists regarding service navigation and emerging comorbidities. A shared care model integrating DB and mental health specialists into primary care might be one approach that warrants implementation and research.

Improving the quality of primary care for adults with intellectual and developmental disabilities: Value of the periodic health examination.

OBJECTIVE: To implement a Health Check protocol for patients with intellectual and developmental disabilities (IDD) and assess outcomes. DESIGN: Retrospective chart review and staff survey. SETTING: Two Ontario family health teams. PARTICIPANTS: Of 276 patients with IDD identified, 139 received the Health Check (Health Check group). A convenience sample (N = 147) of clinical staff participated in the survey. MAIN OUTCOME MEASURES: The protocol included patient identification, invitation, and modified health examination. Chart review assessed completion of 8 preventive maneuvers, and clinical staff were surveyed on their comfort, knowledge, and skills in care of patients with IDD. Logistic regression analyses were used to compare outcomes for the Health Check and non-Health Check groups, adjusted for practice site. RESULTS: Documentation of blood pressure, weight, body mass index, and influenza vaccination was significantly higher (P < .001) in the Health Check group, exceeding 70% of patients. Screening rates were higher for mammograms (63% vs 54%), fecal occult blood testing (39% vs 23%), and diabetes testing (80% vs 61%), but not significantly so, and they were similar to general population rates. Papanicolaou test rates were low for both groups (34% vs 32%). Staff comfort and skills were rated significantly higher (P < .05) for those who performed the Health Check. Still, fewer than half thought they had the necessary skills and resources to care for patients with IDD. CONCLUSION: Performing the Health Check was associated with improved preventive care and staff experience. Wider implementation and evaluation is needed, along with protocol adjustments to provide more support to staff for this work.

Health checks for adults with intellectual and developmental disabilities in a family practice.

OBJECTIVE: To provide tips and tools for primary care practitioners carrying out health checks for adult patients with intellectual and developmental disabilities (IDD) and for implementing a systematic program of health checks in a group or team practice. SOURCES OF INFORMATION: The "Primary Care of Adults with Intellectual and Developmental Disabilities. 2018 Canadian Consensus Guidelines" literature review and interdisciplinary input. Experience in implementing health checks in family practices was obtained through the primary care project of H-CARDD (Health Care Access Research and Developmental Disabilities). MAIN MESSAGE: Annual comprehensive health assessments ("health checks") are a recommendation of the 2018 Canadian consensus guidelines for primary care of adults with IDD because of evidence of benefit in this population. Although health checks might require more time to complete for people with IDD than is usual for encounters in primary care, family physicians are in an ideal position to provide this service because of the attributes of family medicine, which include both an orientation to proactive care and the ability to provide continuity of care. Tips and tools are provided for carrying out health checks for adult patients with IDD and for implementing a systematic program of health checks in a group or team practice. CONCLUSION: Health checks can help enhance a family physician's approach to providing care for adults with IDD.

HELP for behaviours that challenge in adults with intellectual and developmental disabilities.

OBJECTIVE: To provide primary care physicians with an understanding of the causes of behaviours that challenge (BTC) in adults with intellectual and developmental disabilities (IDD), as presented in the 2018 Canadian consensus guidelines for primary care of adults with IDD; to offer a systematic approach to the assessment and treatment of such behaviours; and to link to tools to support these assessments. SOURCES OF INFORMATION: This review elaborates upon guidelines 26 to 29 in the mental health section of the 2018 Canadian consensus guidelines. Several of the authors participated in the development of these guidelines, which were based on literature searches and interdisciplinary input. MAIN MESSAGE: Most adults with IDD are followed by primary care providers but they comprise a small proportion of primary care practices. Unique ways of communicating needs, diagnostic queries, and BTC are common in this population. This complexity can lead to missed diagnoses and inappropriate antipsychotic medication use with attendant risks. This article presents a systematic approach, HELP, to the assessment and treatment of factors of Health, Environment, Lived experience, and Psychiatric conditions that can lead to BTC and includes tools to support these assessments. CONCLUSION: A structured approach to the assessment and treatment of BTC in adults with IDD helps family physicians provide guideline-directed, individualized care to this population. This includes a systematic evaluation using the HELP framework that takes place over multiple visits. A team of health professionals might be needed for optimal care, but these resources are not routinely available across Canada.

EFFECTS OF MOUTHING AND INTERLOCUTOR PRESENCE ON MOVEMENTS OF VISIBLE VS. NON-VISIBLE ARTICULATORS.

Speakers take into account what information a conversation partner requires in a given context in order to best understand an utterance. Despite growing evidence showing that movements of visible articulators such as the lips are augmented in mouthed speech relative to vocalized speech, little to date has been done comparing this effect in visible vs. non-visible articulators. In addition, no studies have examined whether interlocutor engagement differentially impacts these. Building on a basic present/not-present design, we investigated whether presence of audible speech information and/or an interlocutor affect the movements of the lips and the tongue. Participants were asked to a) speak or b) mouth three target syllables in interlocutor-present and interlocutor-not-present conditions, while lip and tongue movements were recorded using video and ultrasound imaging. Results show that lip protrusion was greater in mouthed conditions compared to vocalized ones and tongue movements were either attenuated (/wa/) or unaffected (/ri/, /ra/) by these same conditions, indicating differential effects for the visible and non-visible articulators in the absence of an auditory signal. A significant interaction between the social engagement and vocalizing conditions in reference to lip aperture showed that participants produced smaller lip apertures when vocalizing alone, as compared to when in the presence of an interlocutor. However, measures of lip protrusion failed to find an effect of social engagement. We conclude that speakers make use of both auditory and visual modalities in the presence of an interlocutor, and that when acoustic information is unavailable, compensatory increases are made in the visual domain. Our findings shed new light on the multimodal nature of speech, and pose new questions about differential adaptations made by visible and non-visible articulators in different speech conditions.

Les locuteurs prennent en compte l'information qu'un partenaire de conversation nécessite pour mieux comprendre une expression. Malgré l'évidence grandissante que les mouvements d'articulateurs visibles (comme les lèvres) sont augmentés dans l'articulation silencieuse par rapport à l'articulation vocalisée, peux d'études ont comparé cet effet dans les articulateurs visibles contre les articulateurs non visibles. De plus, aucune étude n'a examiné si l'engagement de l'interlocuteur changera ces résultats. En élaborant un conception d'expérience présent/non présent, nous avons testé si la présence d'information audible et/ou d'un interlocuteur affecte les mouvements des lèvres et de la langue. Les participants ont parlé trois syllabes, avec et sans production audible, dans chacune des conditions interlocuteur-présent et interlocuteur-non présent. Les mouvements des lèvres et de la langue étaient enregistrés avec la vidéo et l'échographie. Nos résultats montrent que la protubérance des lèvres était plus grande dans les conditions non audibles par rapport à ceux audibles et que les mouvements de la langue étaient atténués (/wa/) ou non affectés (/ri/, /ra/) par ces mêmes conditions, indiquant les effets différents pour les articulateurs visibles et non-visibles dans l'absence d'un signal auditif. Une interaction significative entre les conditions d'engagement sociale et d'audibilité de vocalisation avec référence à la fermeture orale a montré que les participants ont produit des fermetures plus étroites dans les conditions de vocalisation audible, interlocuteur-non présent (par rapport à la condition interlocuteur-présent). Cependant, les mesures de protubérance des lèvres n'étaient pas affectées par condition d'engagement sociale. Nous concluons que les locuteurs utilisent à la fois les modalités auditives et visuelles dans la présence d'un interlocuteur, et lorsque l'information acoustique n'est pas disponible, les augmentations compensatoires sont réalisés dans le domain visuel. Nos résultats soulignent encore le caractère multimodal de discours, et posent des nouvelles questions au sujet des adaptations différentielles faites par les articulateurs visibles et non visibles dans les différentes conditions de parole.

Improving capacity to care for patients with intellectual and developmental disabilities: The value of an experiential learning model for family medicine residents.

BACKGROUND: Patients with intellectual and developmental disabilities (IDD) are more likely to experience poor health outcomes and family physicians receive inadequate training to provide appropriate care to this patient group. Little prior research has studied how to effectively train family physicians to care for patients with IDD. OBJECTIVE: The aim of this pilot study was to assess the value of adding an experiential component to didactic education strategies to improve family medicine resident perceived comfort, skills and knowledge related to caring for patients with IDD. METHODS: Structured education programs for residents were implemented at three primary care practices in Ontario, Canada. Two practices received didactic information only (didactic-only group); one received didactic information and an experiential training model including clinical interactions and a written reflection on that experience (didactic plus experiential group). In this separate-sample pre-post design, residents were invited to complete a brief anonymous survey prior to and following the training assessing their perceived comfort, skills and knowledge related to patients with IDD. RESULTS: At baseline, there were no significant differences between the two groups of residents. At follow up, the experiential group reported significantly higher levels of comfort, skills, and knowledge compared to baseline for most items assessed, while in the didactic-only group most items showed little or no improvement. CONCLUSION: This pilot study suggests that providing residents the opportunity to participate in clinical encounters with patients with IDD, as well as a structured process to reflect on such encounters, results in greater benefit than didactic training alone.

Playing With Code: An Innovative Way to Teach Numeracy and Early Math Concepts to Young DHH Children in the 21st Century.

While focusing on numeracy is essential in preschool classrooms with deaf and hard of hearing (DHH) children, it is also important that concepts of numeracy be taught in a way that incorporates executive functions, introduces computational thinking, and prepares students for life in a 21st-century world. Technology-enhanced teaching resources (e.g., Code-a-pillar, Bee-Bot, Kubo) provide coding opportunities that engage young children in problem solving, planning, and organization. These tools provide kinesthetic experiences in the exploration of early numeracy skills like counting, addition, subtraction, and estimation. The present article provides a rationale for including 21st-century teaching practices and educational technology resources in preschool classrooms with DHH children as one path toward strengthening early mathematics understanding. The authors also offer tips for teachers on how to select technology tools for classroom use and ways to integrate the use of these tools as part of meaningful mathematics instruction.

ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.

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.

Evaluating the Implementation of Health Checks for Adults With Intellectual and Developmental Disabilities in Primary Care: The Importance of Organizational Context.

Compared to other adults, those with intellectual and developmental disabilities have more health issues, yet are less likely to receive preventative care. One strategy that has shown success in increasing prevention activities and early detection of illness is the periodic comprehensive health assessment (the health check). Effectively moving evidence into practice is a complex process that often receives inadequate attention. This qualitative study evaluates the implementation of the health check at two primary-care clinics in Ontario, Canada, and the influence of the clinic context on implementation decisions. Each clinic implemented the same core components; however, due to contextual differences, some components were operationalized differently. Adapting to the setting context is important to ensuring successful and sustainable implementation.

Safety and feasibility of modified chair-yoga on functional outcome among elderly at risk for falls.

Falls are among the most common problems affecting older adults. At least 50% of those over the age of 80 fall annually. The goal of this pilot study was to assess the safety and feasibility of structured yoga in an elderly population with fall risk. Seniors at risk for falls were identified and enrolled in a single arm pilot trial. A chair based yoga program was provided twice a week for 8 weeks. The program was designed from previously published pilot data. A battery of validated instruments was administered at baseline and week eight and was used to identify which instruments may be sensitive to change as a result of a yoga program. Among sixteen seniors (median age of 88) with a previous history of falls, 87% provided data for assessment at the end of the intervention. Two patients withdrew, one due to a fall outside the institution and the other due to lack of time and interest. There were no adverse events during the yoga sessions. Paired-t tests compared pre-post changes and gains were noted in Fear of Falling (5.27 to 2.60; P = 0.029) and SPPB sit to stand subscale (0.31 to 1.00; P =.022). Improved trends were noted in anxiety and the timed up and go assessments. We found the modified chair-yoga program is safe and recruitment is feasible. Our data suggests that yoga may be beneficial in improving mobility and reducing fear of falling which warrants additional research via randomized controlled trial.