RESUMO
Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial targeting. Building upon our experiences targeting CD19 and CD22 in B-cell acute lymphoblastic leukemia (B-ALL), we report on our phase 1 dose-escalation study of a novel murine stem cell virus (MSCV)-CD19/CD22-4-1BB bivalent CAR T-cell (CD19.22.BBζ) for children and young adults (CAYA) with B-cell malignancies. Primary objectives included toxicity and dose finding. Secondary objectives included response rates and relapse-free survival (RFS). Biologic correlatives included laboratory investigations, CAR T-cell expansion and cytokine profiling. Twenty patients, ages 5.4 to 34.6 years, with B-ALL received CD19.22.BBζ. The complete response (CR) rate was 60% (12 of 20) in the full cohort and 71.4% (10 of 14) in CAR-naïve patients. Ten (50%) developed cytokine release syndrome (CRS), with 3 (15%) having ≥ grade 3 CRS and only 1 experiencing neurotoxicity (grade 3). The 6- and 12-month RFS in those achieving CR was 80.8% (95% confidence interval [CI]: 42.4%-94.9%) and 57.7% (95% CI: 22.1%-81.9%), respectively. Limited CAR T-cell expansion and persistence of MSCV-CD19.22.BBζ compared with EF1α-CD22.BBζ prompted laboratory investigations comparing EF1α vs MSCV promoters, which did not reveal major differences. Limited CD22 targeting with CD19.22.BBζ, as evaluated by ex vivo cytokine secretion and leukemia eradication in humanized mice, led to development of a novel bicistronic CD19.28ζ/CD22.BBζ construct with enhanced cytokine production against CD22. With demonstrated safety and efficacy of CD19.22.BBζ in a heavily pretreated CAYA B-ALL cohort, further optimization of combinatorial antigen targeting serves to overcome identified limitations (www.clinicaltrials.gov #NCT03448393).
Assuntos
Linfoma de Burkitt , Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Animais , Antígenos CD19 , Síndrome da Liberação de Citocina , Citocinas , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Camundongos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Recidiva , Linfócitos TRESUMO
Background: Given the rapid increase in telehealth utilization, health care providers are being increasingly trained to deliver services virtually. However, there are limited measures available to assess the extent to which structured trainings influence competency domains associated with telehealth delivery. Methods: The authors developed the Telehealth Competency Questionnaire-Provider (TCQ-P) using a multistep process, including a literature review and expert reviewers. Using two datasets, we used exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to validate and refine the tool, respectively. The final version contained 17 items. Model fit was evaluated using the comparative fit index (CFI) (>0.90), Tucker-Lewis index (TLI) (>0.80), standardized root mean square residual (SRMR) (<0.08) and root mean square of error of approximation (RMSEA) (<0.08). Results: Participants included n = 701 in the exploratory study and n = 721 in the confirmatory study. Two items were revised, and one item was deleted as a result of the EFA, and the CFA of 17 number of items supported a 3-factor model (i.e., Evaluation, Rapport, Troubleshooting). Model fit was good, with CFI = 0.984, TLI = 0.978, RMSEA = 0.051, and SRMR = 0.035. Discussion: The TCQ-P measures three essential domains of telehealth competency, which is essential for future health care providers. The measure may be used to assess telehealth training outcomes.
Assuntos
Telemedicina , Humanos , Telemedicina/normas , Inquéritos e Questionários , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Competência Clínica , Pessoal de Saúde , Análise Fatorial , Reprodutibilidade dos Testes , PsicometriaRESUMO
In recent years, there has been increased interest in completing occupational therapy doctoral capstones with people experiencing homelessness. Given the complexity of practice with this population and its history of discrimination and marginalization, we argue for the development of guidelines for completing capstones in unhoused settings. In this column, we present background and contextual information, justification for the need for guidelines, and preliminary recommendations for consideration by students and faculty. Our aim is to invite reflection within the profession and among academic institutions and to promote dialogue with community agencies that serve this population to ensure that capstones are developed ethically, sustainably, and without unintentionally perpetuating harm.
Assuntos
Pessoas Mal Alojadas , Terapia Ocupacional , Humanos , Terapia Ocupacional/normas , Guias de Prática Clínica como AssuntoRESUMO
IMPORTANCE: Occupational therapy practitioners need evidence to support interventions that promote subjective well-being among autistic people and their families through optimal engagement and participation in occupations. OBJECTIVE: These Practice Guidelines are informed by systematic reviews to expand knowledge of interventions that promote access, inclusion, engagement, and optimal participation in occupations that are meaningful to autistic people. Our intent was to foster occupational therapy practitioners' clinical decision-making and reasoning when working with autistic people and their care partners. METHOD: These Practice Guidelines were developed on the basis of four systematic reviews, supporting evidence and literature, along with continued revisions and integration through an iterative and collaborative process. RESULTS: A total of 98 articles were included in the systematic reviews, which are the foundation for practice recommendations in these guidelines. Forty-eight of the systematic review articles were used to inform the clinical recommendations included in these Practice Guidelines. CONCLUSIONS AND RECOMMENDATIONS: Strong to moderate evidence indicates the need for multidisciplinary, goal-oriented interventions to support autistic people in different contexts. Although there is only emerging evidence in the inclusion of autistic people's strengths, interests, and perspectives to guide occupational therapy interventions, such practices can enhance the delivery of neurodiversity-affirming and trauma-informed practices. In addition, evidence is needed to support participation in activities of daily living (ADLs) for autistic youths. We recommend the use of strengths-based language to describe autistic people and the use of environmental adaptations, care partner education, and coaching to enhance occupational therapy service delivery. Plain-Language Summary: The literature is sparse regarding neurodiversity-affirming and trauma-informed practices for autistic youths, as well as for participation in activities of daily living (ADLs). These Practice Guidelines provide new information on positive mental health development; self-determination; ADLs, instrumental ADLs, play, and leisure occupations for children, adolescents, and adults; person-centered planning for adolescents and adults; and rest and sleep. Information on health management is also provided. Positionality Statement: This article uses the identity-first language autistic people. This nonableist language describes their strengths and abilities and is a conscious decision. This language is favored by autistic communities and self-advocates and has been adopted by health care professionals and researchers (Bottema-Beutel et al., 2021; Kenny et al., 2016). However, we respect the use of person-first language and have made a conscious decision to include research articles that have used this language.
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Transtorno Autístico , Terapia Ocupacional , Humanos , Atividades Cotidianas , Transtorno Autístico/reabilitaçãoRESUMO
Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from the systematic review on interventions to support participation in sleep for autistic1 children and adolescents (birth to 18 yr).
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Transtorno Autístico , Terapia Ocupacional , Revisões Sistemáticas como Assunto , Adolescente , Criança , Humanos , Prática Clínica Baseada em Evidências , SonoRESUMO
Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from the systematic review on interventions to support autistic1 children and youth (up to 18 yr old) and focuses on participation in education settings.
Assuntos
Transtorno Autístico , Terapia Ocupacional , Adolescente , Criança , Humanos , Prática Clínica Baseada em Evidências , Estudantes , Revisões Sistemáticas como AssuntoRESUMO
Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from the systematic review on interventions to support participation in basic and instrumental activities of daily living by autistic1 children and adolescents (birth to 18 yr).
Assuntos
Transtorno Autístico , Terapia Ocupacional , Criança , Humanos , Adolescente , Atividades Cotidianas , Prática Clínica Baseada em EvidênciasRESUMO
Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings to support participation in play for autistic1 children and adolescents (birth to 18 yr).
RESUMO
Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from clinic-based studies to support social participation for autistic1 children and adolescents (birth to 18 yr).
Assuntos
Transtorno Autístico , Terapia Ocupacional , Adolescente , Criança , Humanos , Participação Social , Revisões Sistemáticas como AssuntoRESUMO
Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings to support social participation in school contexts for autistic1 children and adolescents (birth to 18 yr).
Assuntos
Transtorno Autístico , Terapia Ocupacional , Adolescente , Criança , Humanos , Instituições Acadêmicas , Participação Social , Revisões Sistemáticas como AssuntoRESUMO
Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings to support social participation for autistic1 children and adolescents (birth to 18 yr) in homes and communities.
Assuntos
Transtorno Autístico , Terapia Ocupacional , Adolescente , Criança , Humanos , Participação Social , Revisões Sistemáticas como AssuntoRESUMO
Serious bacterial infections (SBI) can lead to devastating complications with CD19 CAR T cells and cytokine release syndrome (CRS). Little is known about consequences of and risk factors for SBI with novel CAR T-cell constructs or with CRS complicated by HLH-like toxicities. We report on three patients with B-cell acute lymphoblastic leukemia treated with CD22 CAR T cells who developed SBI and CRS-associated HLH. Serum cytokine profiling revealed sustained elevations well beyond CRS resolution, suggesting ongoing systemic inflammation. Heightened inflammatory states converging with SBI contribute to poor outcomes, and recognition and prevention of extended inflammation may be needed to improve outcomes.
Assuntos
Bacteriemia , Síndrome da Liberação de Citocina , Linfo-Histiocitose Hemofagocítica , Antígenos CD19 , Bacteriemia/imunologia , Bacteriemia/microbiologia , Síndrome da Liberação de Citocina/imunologia , Humanos , Imunoterapia Adotiva , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/microbiologia , Receptores de Antígenos Quiméricos , Linfócitos TRESUMO
OBJECTIVE: To assess differences in sensory processing patterns between children with chronic constipation compared with a matched normative sample as well as to examine the extent to which specific sensory processing patterns and modality scores predicted atypical toileting behaviors. STUDY DESIGN: We used a cross-sectional comparative design to evaluate differences between children age 3 and 5 years old with constipation (n = 66) and those in a matched control sample (n = 66). We also examined the contribution of sensory processing patterns to atypical toileting behavior in the clinical sample. RESULTS: Children with chronic constipation showed significantly higher sensory scores than a matched normative sample, specifically in oral processing (P < .001), visual processing (P < . 05), sensory avoiding (P < .001), and sensory sensitivity (P < .05). Sensory registration, avoidance, and oral processing significantly predicted toileting behavior over-responsiveness, and attentional difficulties contribute to toileting under-responsiveness. CONCLUSIONS: Our findings revealed that children with chronic constipation have underlying sensory characteristics that contribute to toileting behavioral difficulties. By identifying sensory processing patterns of children with chronic constipation, we can optimize behavioral interventions to complement laxative therapy for this population.
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Doença Crônica , Constipação Intestinal/fisiopatologia , Sensação/fisiologia , Limiar Sensorial/fisiologia , Estudos de Casos e Controles , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Natural contexts and family involvement are key features of effective intervention approaches. However, the measurement of community participation and parent engagement with children remains complex. Therefore, we examined the feasibility of combining use of the Language ENvironment Analysis (LENA®) system and a global positioning system (GPS; i.e., Qstarz® BT-Q1000XT). The LENA is a small speech recognition device that captures and quantifies full-day recordings of the natural language environment. The Qstarz BT-Q1000XT is a wearable GPS data logger that allows identification of the locations a person visits. The marrying of these measures allows for an accurate representation of community settings that afford children greater social communication opportunities. Our results show that the combination of measures provides meaningful social communication location data. Also, the participating caregiver reported that the collection of measures was feasible across community settings.
Assuntos
Desenvolvimento Infantil , Comunicação , Participação da Comunidade , Família , Terapia Ocupacional/instrumentação , Pré-Escolar , Sistemas de Informação Geográfica , Humanos , MasculinoRESUMO
Sensory processing is a personal trait that can contribute to challenging behavior. Protective factors, such as resiliency, can support children in managing their behavior, yet little research has addressed the contribution of sensory processing to protective factors. Therefore, in this cross-sectional study we aimed to determine the contribution of sensory processing (using the Sensory Profile-2) to challenging behavior and protective factors (using the Behavior Assessment System for Children, 2nd ed., Parent Rating Scales) in a sample of 51 children ages 6-11 yr from the general U.S. POPULATION: The results indicated that sensory avoiding predicts externalizing behaviors, depression, resiliency, and adaptability. In addition, sensory seeking is related to depression and resiliency, whereas sensory sensitivity is related to externalizing behaviors. Implications for occupational therapy research and practice are discussed.
Assuntos
Transtornos do Comportamento Infantil/psicologia , Ajustamento Emocional , Desempenho Psicomotor , Resiliência Psicológica , Criança , Desenvolvimento Infantil , Estudos Transversais , Feminino , Humanos , Masculino , Terapia Ocupacional , Psicometria , Estados UnidosRESUMO
OBJECTIVE: We investigated the efficacy of Occupation-Based Coaching delivered via telehealth for families of young children with autism spectrum disorder (ASD). METHOD: Participants were 18 families of children with ASD ages 2-6 yr. We used descriptive statistics to understand intervention characteristics and paired-sample t tests to examine changes in parent efficacy and child participation. RESULTS: Parents identified many areas of child adaptive behavior as intervention goals. Results showed that parent efficacy and various domains of child participation significantly increased postintervention (both ps < .05). Additionally, children showed significant gains in parent-identified goals. CONCLUSION: Occupation-Based Coaching delivered via telehealth appears to be an effective method of intervention to increase parent efficacy and child participation among families of children with ASD. Occupational therapists may consider how telehealth may be used to provide intervention to an increased number of families, in particular those in underserved areas.
Assuntos
Transtorno do Espectro Autista/reabilitação , Tutoria , Relações Pais-Filho , Poder Familiar , Telemedicina , Adulto , Criança , Pré-Escolar , Atenção à Saúde/métodos , Família , Feminino , Humanos , Masculino , Terapia Ocupacional , Pais , Planejamento de Assistência ao Paciente , Participação do Paciente , Jogos e BrinquedosRESUMO
AIMS: The purpose of this study was to examine sensory processing in children ages 3-14 years with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and typical development (TD) using the Sensory Profile 2nd Edition (Dunn, 2014). METHODS: Participants included 239 children (ASD = 77; ADHD = 78; TD = 84) matched on age and gender. Multivariate analysis of covariance was used to compare the extent to which the three grsoups differed on sensory processing patterns (i.e., sensitivity, avoiding, registration, seeking) and sensory systems (i.e., auditory, visual, touch, movement, body position, oral, conduct, attention, social). We also examined the effect of chronological age. RESULTS: Children with ASD and ADHD did not differ in sensory processing patterns which were elevated as compared to a TD group. Children with ASD showed the highest rate of oral processing differences, followed by ADHD and TD. Children with ADHD had higher visual processing scores than children with ASD and TD. Older children had lower scores for seeking, auditory, visual, movement, touch, and conduct than younger children, regardless of diagnosis. CONCLUSIONS: Findings suggest that sensory features may be an area of overlap of behaviors in ASD and ADHD, which may have implications for intervention approaches for children with these conditions.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Desenvolvimento Infantil/fisiologia , Sensação/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , MasculinoRESUMO
AIMS: This mixed methods study examined: 1) how young children with and without developmental disabilities and delays participate in daycare or preschool activities; 2) similarities and differences in environmental factors impacting daycare or preschool participation; and 3) strategies used by parents who desired a change in their child's participation. METHODS: Data were drawn from 129 parents of young children with and without developmental disabilities and delays (mean age = 49.3 months) residing in North America. Summary and item-level group differences based on disability status were assessed for participation and environmental supports to participation. Narrative data on parental strategies were content coded, transformed into numerical counts, and summarized to identify strategies commonly employed by parents to promote their child's participation. RESULTS: Moderate to large disability related group differences in participation and environmental support to participation were found even after controlling for confounding effects of child age, child gender, and family income. Parents commonly described strategies focused on "child care tasks" and "child peer groups," irrespective of the type(s) of change they desired. CONCLUSIONS: Study findings suggest that discrepancies in school participation between young children with and without disabilities and delays can be detected and intervened on during the early childhood period.
Assuntos
Deficiências do Desenvolvimento , Crianças com Deficiência/psicologia , Pais/psicologia , Participação Social , Criança , Creches , Pré-Escolar , Estudos Transversais , Deficiências do Desenvolvimento/psicologia , Avaliação da Deficiência , Crianças com Deficiência/educação , Feminino , Humanos , Lactente , Masculino , Percepção , Escolas Maternais , Meio Social , Apoio Social , Inquéritos e QuestionáriosRESUMO
Children with autism spectrum disorder often demonstrate unusual behavioral responses to sensory stimuli (i.e., sensory features). To manage everyday activities, caregivers may implement strategies to address these features during family routines. However, investigation of specific strategies used by caregivers is limited by the lack of empirically developed measures. In this study, we describe the development and pilot results of the Caregiver Strategies Inventory (CSI), a supplement to the Sensory Experiences Questionnaire Version 3.0 (SEQ 3.0; Baranek, 2009) that measures caregivers' strategies in response to their children's sensory features. Three conceptually derived and empirically grounded strategy types were tested: cognitive-behavioral, sensory-perceptual, and avoidance. Results indicated that the CSI demonstrated good internal consistency and that strategy use was related to child age and cognition. Moreover, parent feedback after completing the CSI supported its utility and social validity. The CSI may be used alongside the SEQ 3.0 to facilitate a family-centered approach to assessment and intervention planning.
Assuntos
Transtorno do Espectro Autista/enfermagem , Cuidadores , Pais , Transtornos da Percepção/enfermagem , Adolescente , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transtornos da Percepção/psicologia , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
Sensory processing differences in preschool-age children with autism spectrum disorder (ASD) affect their engagement in everyday activities, thereby influencing opportunities to practice and develop skills such as social communication and adaptive behavior. The purpose of this study was to investigate the extent to which specific sensory processing patterns relate to aspects of development (i.e., adaptive behavior, expressive and receptive language, fine and gross motor skills, social behavior) in a sample of preschool-age children with ASD (N=400). A retrospective chart review was used to gather clinical data. Results suggest that sensory processing patterns differentially affect children's developmental skills and adaptive behavior. Certain sensory processing patterns predicted children's development of language, motor, and adaptive skills. These findings have clear implications for occupational therapy practice with young children with ASD. Practitioners should consider how sensory processing in ASD both supports and limits children's ability to engage in social communication and learning opportunities.