Browsing by Author "Franz, Lauren"
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Item Open Access A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder.(The Journal of pediatrics, 2020-07) Dawson, Geraldine; Sun, Jessica M; Baker, Jennifer; Carpenter, Kimberly; Compton, Scott; Deaver, Megan; Franz, Lauren; Heilbron, Nicole; Herold, Brianna; Horrigan, Joseph; Howard, Jill; Kosinski, Andrzej; Major, Samantha; Murias, Michael; Page, Kristin; Prasad, Vinod K; Sabatos-DeVito, Maura; Sanfilippo, Fred; Sikich, Linmarie; Simmons, Ryan; Song, Allen; Vermeer, Saritha; Waters-Pick, Barbara; Troy, Jesse; Kurtzberg, JoanneObjective
To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD).Study design
This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion.Results
CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power.Conclusions
Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.Item Open Access A Qualitative Study of Contextual Factors’ Impact on the Adaptation of a Caregiver-mediated Early Autism Intervention in South Africa(2016) Guler, JessyBackground: Autism Spectrum Disorder (ASD) is a major global health challenge as the majority of individuals with ASD live in low- and middle-income countries (LMICs) and receive little to no services or support from health or social care systems. Despite this global crisis, the development and validation of ASD interventions has almost exclusively occurred in high-income countries, leaving many unanswered questions regarding what contextual factors would need to be considered to ensure the effectiveness of interventions in LMICs. This study sought to conduct explorative research on the contextual adaptation of a caregiver-mediated early ASD intervention for use in a low-resource setting in South Africa.
Methods: Participants included 22 caregivers of children with autism, including mothers (n=16), fathers (n=4), and grandmothers (n=2). Four focus groups discussions were conducted in Cape Town, South Africa with caregivers and lasted between 1.5-3.5 hours in length. Data was recorded, translated, and transcribed by research personnel. Data was then coded for emerging themes and analyzed using the NVivo qualitative data analysis software package.
Results: Nine contextual factors were reported to be important for the adaptation process including culture, language, location of treatment, cost of treatment, type of service provider, familial needs, length of treatment, support, and parenting practices. One contextual factor, evidence-based treatment, was reported to be both important and not important for adaptation by caregivers. The contextual factor of stigma was identified as an emerging theme and a specifically relevant challenge when developing an ASD intervention for use in a South African context.
Conclusions: Eleven contextual factors were discussed in detail by caregivers and examples were given regarding the challenges, sources, and preferences related to the contextual adaptation of a parent-mediated early ASD intervention in South Africa. Caregivers reported a preference for an affordable, in-home, individualized early ASD intervention, where they have an active voice in shaping treatment goals. Distrust of community-based nurses and health workers to deliver an early ASD intervention and challenges associated with ASD-based stigma were two unanticipated findings from this data set. Implications for practice and further research are discussed.
Item Open Access A tablet-based game for the assessment of visual motor skills in autistic children.(NPJ digital medicine, 2023-02) Perochon, Sam; Matias Di Martino, J; Carpenter, Kimberly LH; Compton, Scott; Davis, Naomi; Espinosa, Steven; Franz, Lauren; Rieder, Amber D; Sullivan, Connor; Sapiro, Guillermo; Dawson, GeraldineIncreasing evidence suggests that early motor impairments are a common feature of autism. Thus, scalable, quantitative methods for measuring motor behavior in young autistic children are needed. This work presents an engaging and scalable assessment of visual-motor abilities based on a bubble-popping game administered on a tablet. Participants are 233 children ranging from 1.5 to 10 years of age (147 neurotypical children and 86 children diagnosed with autism spectrum disorder [autistic], of which 32 are also diagnosed with co-occurring attention-deficit/hyperactivity disorder [autistic+ADHD]). Computer vision analyses are used to extract several game-based touch features, which are compared across autistic, autistic+ADHD, and neurotypical participants. Results show that younger (1.5-3 years) autistic children pop the bubbles at a lower rate, and their ability to touch the bubble's center is less accurate compared to neurotypical children. When they pop a bubble, their finger lingers for a longer period, and they show more variability in their performance. In older children (3-10-years), consistent with previous research, the presence of co-occurring ADHD is associated with greater motor impairment, reflected in lower accuracy and more variable performance. Several motor features are correlated with standardized assessments of fine motor and cognitive abilities, as evaluated by an independent clinical assessment. These results highlight the potential of touch-based games as an efficient and scalable approach for assessing children's visual-motor skills, which can be part of a broader screening tool for identifying early signs associated with autism.Item Open Access Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial.(Stem cells translational medicine, 2017-05) Dawson, Geraldine; Sun, Jessica M; Davlantis, Katherine S; Murias, Michael; Franz, Lauren; Troy, Jesse; Simmons, Ryan; Sabatos-DeVito, Maura; Durham, Rebecca; Kurtzberg, JoanneDespite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed. We hypothesized that umbilical cord blood-derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain. Accordingly, we conducted a phase I, open-label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials. Twenty-five children, median age 4.6 years (range 2.26-5.97), with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit, were enrolled. Children were evaluated with a battery of behavioral and functional tests immediately prior to cord blood infusion (baseline) and 6 and 12 months later. Assessment of adverse events across the 12-month period indicated that the treatment was safe and well tolerated. Significant improvements in children's behavior were observed on parent-report measures of social communication skills and autism symptoms, clinician ratings of overall autism symptom severity and degree of improvement, standardized measures of expressive vocabulary, and objective eye-tracking measures of children's attention to social stimuli, indicating that these measures may be useful endpoints in future studies. Behavioral improvements were observed during the first 6 months after infusion and were greater in children with higher baseline nonverbal intelligence quotients. These data will serve as the basis for future studies to determine the efficacy of umbilical cord blood infusions in children with ASD. Stem Cells Translational Medicine 2017;6:1332-1339.Item Open Access Caregiver Descriptions of Joint Activity Routines and Perceptions of Acceptability of a Caregiver Coaching Approach to Early Autism Spectrum Disorder Intervention in South Africa(2018) Ramseur II, Kevin ChristopherBackground: Early detection and early intervention for autism spectrum disorder (ASD) is critical because it can reduce the severity of core ASD symptoms, and result in significant long-term improvements in language acquisition, social skills, cognitive abilities, and adaptive behaviors. Involving caregivers in the delivery of early ASD intervention is becoming increasingly important, particularly in low-resource settings, due to limited access to specialist ASD services. Currently, there is no published research on early ASD intervention in South Africa or sub-Saharan Africa (SSA). In addition, there are no published descriptions of caregiver-child joint activity routines, in which early intervention techniques can be embedded, or perceptions of the acceptability of a caregiver coaching approach.
Study Aims: This study aimed to elicit qualitative descriptions of caregiver-child joint activity routines in order to understand how the Early Start Denver Model (ESDM), an evidence-based early ASD intervention, could fit in a low resource South African setting. It also aimed to gauge the acceptability of a caregiver coaching intervention from South African caregivers of young children with ASD who received two taster sessions of caregiver coaching.
Methods: Participants were recruited from the Western Cape Education Department autism waiting list through convenience sampling. Four focus group discussions were conducted with 22 caregivers of young children with ASD, which gathered data on caregiver-child joint activity routines. Four additional families were recruited to participate in two caregiver coaching sessions each. Four in-depth interviews were subsequently conducted with the six caregivers from these families, which gathered data on joint activity routines and acceptability of a caregiver coaching intervention. Data were analyzed through a qualitative content analysis approach, which used a combination of inductive and deductive methods to determine the salient themes and subthemes within the data.
Results: Caregiver descriptions of joint activity routines aligned with ESDM themes of object-based play, sensory social routines, and family routines. In object-based play caregivers reported engaging in turn-taking with their children, teaching skills across developmental domains, embracing child-directed activities, and managing challenges related to play in resource limited settings. In sensory social routines, caregivers described physical play, an awareness of the child’s affect and engagement, increased child expressive communication, and willingness of the child to engage with different play partners. In family routines, caregivers reported child participation in meals and bath time. Caregivers reported that a caregiver coaching approach was acceptable and that they had acquired a variety of skills, including strategies to enhance their child’s social communication. Caregivers preferred receiving coaching in their homes as opposed to in a clinic setting; however, limitations in physical space and financial resources were important considerations.
Conclusion: Training caregiver coaches and non-specialist workers narrows the treatment gap by providing access to children in need of early ASD intervention. This is essential, because of the scarcity of psychologists and psychiatrists working in mental health in low and middle-income countries (LMIC). Descriptions from South African caregivers of caregiver-child joint activity routines and acceptability of the caregiver coaching approach contextualize the caregiver coaching intervention. These data will inform the adaptation and piloting of an early ASD intervention within a low-resource South African setting.
Item Open Access Caregiver descriptions of joint activity routines with young children with autism spectrum disorder in South Africa.(Pediatric medicine (Hong Kong, China), 2019-03-13) Ramseur, Kevin; de Vries, Petrus J; Guler, Jessy; Shabalala, Nokuthula; Seris, Noleen; Franz, LaurenBackground:Coaching caregivers to deliver Naturalistic Developmental Behavioral Intervention (NDBI) strategies to their young child with autism spectrum disorder (ASD) could help address the provider capacity barrier in sub-Saharan Africa. However, the behavioral and developmental research that underpins NDBIs is overwhelmingly drawn from high resource settings. Therefore, our understanding of joint activity routines, including play and family routines in which NDBI strategies are embedded, may have limited applicability in low resource, culturally diverse environments. Important questions remain on how to adapt NDBIs to be relevant in the family lives in these settings. This study aimed to elicit descriptions of joint activity routines from caregivers of young children with ASD in South Africa, to understand whether an NDBI-informed caregiver coaching could 'fit' within the multicultural, multilingual South African context. Methods:Four focus groups were conducted with 22 caregivers of young children with ASD who were recruited from the Western Cape Education Department autism waiting list. Data were analyzed through directed content analysis, which uses inductive methods to determine salient themes and subthemes. The predetermined initial coding classifications were based on joint activity routine categories of object-based play, sensory social routines, and family routines. Results:Participants' descriptions of caregiver-child interactions aligned with a-priori joint activity routine categories. During object-based play, caregivers engaged in turn-taking, taught developmental skills (for example cognitive, language, and fine motor skills), and participated in child-directed activities. During sensory social routines, caregivers described active, physical play, awareness of child affect, increased child expressive language, and willingness to engage with different play partners. During family routines, caregivers detailed child participation in mealtime and bath time. Conclusions:These data suggest that South African caregivers of young children with ASD use joint activity routines to engage their children and teach them new skills, thus suggesting a degree of 'fit' between South African caregiver-child interactions and an NDBI-informed caregiver coaching approach. However, more information on family routines and which caregiver interacts with the young child with ASD during these routines would help tailor these interventions for low-resource African settings.Item Open Access Fidelity of caregiver and non-specialist early autism intervention implementation in South Africa(2019) Ding, XiaoxuAbstract
Background: Autism spectrum disorder (ASD), a lifelong neurodevelopmental disorder, is recognized by the World Health Organization as a growing global public health concern (World Health Organization, 2013) and may represent some of the greatest burden of disease in children and adolescents. Although currently there is no known cure for ASD, different levels of recovery are still observed in patients. Early detection and intervention with evidence-based treatment models such as the Early Start Denver Model (ESDM) can improve intellectual ability and adaptive behaviors, and decrease symptom severity and challenging behaviors (Dawson et al, 2010; Rogers et al, 2012; Estes et al., 2015). In addition, early intervention with models such as ESDM can decrease long term costs associated with special education services, sheltered employment and supported living (Cidav et al., 2017). In South Africa a small start has been made on caregiver coaching early autism intervention, where caregivers are taught strategies to enhance their child’s social communication attempts (Franz et al., 2017; Guler et al., 2017). But important question remains as to whether non-specialists can deliver an early autism intervention at fidelity and in doing so impact child social communication and social engagement. Fidelity of intervention delivery is the degree to which programs are implemented as intended by program developers and is important because it is a potential moderator of the effect of the intervention on targeted health outcomes (Carroll et al., 2007; Brownson, Colditz, & Proctor, 2012).
Study Aims: The long-term goal of the study is to advance our understanding of the efficacy of caregiver coaching early autism interventions delivered by non-specialists in low resource settings. The overall aims of this South African study are tracking changes in fidelity of caregiver and non-specialist intervention implementation measured using established ESDM fidelity scales of (a) caregiver implementation of ESDM, and (b) non-specialist caregiver
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coaching techniques during 12 weeks of 1 hour per week P-ESDM coaching in 6 caregiver-child dyads.
Method: The overall study design is a hybrid type 1 effectiveness design. There are twelve 60-minute sessions in total, one hour per week, and all sessions will be video recorded. Each session of non-specialist coaching and caregiver child interaction will be coded at each of the 12 sessions for fidelity of caregiver implementation of ESDM strategies and coaching skills. The data analysis process aims to track changes in the fidelity of caregiver implementation of ESDM and the fidelity of non-specialist caregiver coaching techniques during each of the 12 week of 1 hour per week P-ESDM coaching in 2 caregiver-child dyads. The display fidelity scores visually across session time points, a similar approach used by Vismara (Vismara, Colombi, & Rogers, 2009). In addition, modifications are made to the original plan to adapt local situations to make the intervention more fit to local settings and such modifications are documented using Wiltsey-Stirman framework.
Results: The adaptation process is documented by the Wiltsey-Stirman framework by five categories of modifications on who made the adaptations, what is modified, level of delivery, context of modification and the nature of modification. The fidelity score for each caregiver and coach fidelity rating items are listed and the average fidelity scores for all intervention sessions are also calculated. The worst performing rating items on Caregiver Fidelity Scale are ABC format, joint activity structure and elaboration, quality of dyadic engagement, instructional techniques and application. The worst performing rating items on Coaching Fidelity Scale are greeting and check-in, conversational and reciprocal, reflective, coaching activity 2 and collaborative. There is no significant increasing or decreasing trend of caregiver and coach performances based on average fidelity scores across twelve sessions and
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there are no strong correlation observed between coaching fidelity scores and caregiver fidelity scores.
Conclusion: Training non-specialists and including them as a part of ASD treatment can help to reduce the resources gap by providing accessible and affordable early ASD intervention in lower-resourced settings. Culturally-sensitive adaptations made to the original intervention program are also needed to make the treatment reach its full capacity in a multi-cultural and multi-lingual community like South Africa. There are only two pairs of caregiver, child and non- specialist dyads participated in this pre-pilot study and such lack of sufficient data serves as a major limitation of this study. In subsequent researches, more caregivers and non-specialists shall participate in the study to help with building more systematic adaptation process and generalize the process of reaching intervention fidelity in lower-resourced settings like South Africa. And these types of interventions have the potential to be scaled up in community settings globally and begin to address the needs of young children and families impacted by autism.
Item Open Access Implementing early intervention for autism spectrum disorder: a global perspective.(Pediatric medicine (Hong Kong, China), 2019-08-23) Franz, Lauren; Dawson, GeraldineItem Open Access Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder.(Stem cells translational medicine, 2020-10) Sun, Jessica M; Dawson, Geraldine; Franz, Lauren; Howard, Jill; McLaughlin, Colleen; Kistler, Bethany; Waters-Pick, Barbara; Meadows, Norin; Troy, Jesse; Kurtzberg, JoanneOngoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 106 cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD-specific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial.Item Open Access Key Stakeholder Perspectives on the Feasibility of Implementing Early Childhood Autism Spectrum Disorder (ASD) Interventions in South Africa(2017) Adewumi, KonyinsopeBackground: Autism spectrum disorder (ASD) is a major public health challenge worldwide. Early intensive intervention services have been shown to reduce core ASD symptomatology, but there are many barriers to implementing these services in low resource settings. Training caregivers to deliver intensive early ASD intervention may help to overcome many of the implementation barriers, but there is limited research about the feasibility of delivering a caregiver-mediated early ASD intervention in low resource settings and the compatibility of such interventions with existing platforms of care. Study Aims: This study explored key stakeholder perspectives on the feasibility of implementing early ASD intervention services in the Western Cape Province of South Africa. Methods: Eight in-depth interviews with District and Provincial representatives from the Department of Health, the Department of Education, the Department of Social Development, and two non-governmental organizations were conducted. Results: Stakeholders identified 20 current policies relevant to ASD in South Africa, future directions for ASD policy, and perceived barriers to ASD early intervention services. All participants reported a strong desire for early intervention services and identified key potential facilitators to early intervention. Conclusion: Caregiver mediated early ASD intervention may address barriers to ASD services in the Western. This study identified perceived barriers to such interventions as well as facilitators to delivering a caregiver mediated intervention. Adaptions of caregiver-mediated early ASD interventions in the Western Cape must be affordable, simplified to be delivered by paraprofessionals, and adapted to include local cultural components such as language.
Item Open Access White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Trial Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism.(Stem cells translational medicine, 2019-02) Carpenter, Kimberly LH; Major, Samantha; Tallman, Catherine; Chen, Lyon W; Franz, Lauren; Sun, Jessica; Kurtzberg, Joanne; Song, Allen; Dawson, GeraldineAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social communication deficits and the presence of restricted interests and repetitive behaviors. We have previously reported significant improvements in behavior, including increased social functioning, improved communication abilities, and decreased clinical symptoms in children with ASD, following treatment with a single infusion of autologous cord blood in a phase I open-label trial. In the current study, we aimed to understand whether these improvements were associated with concurrent changes in brain structural connectivity. Twenty-five 2- to 6-year-old children with ASD participated in this trial. Clinical outcome measures included the Vineland Adaptive Behavior Scales-II Socialization Subscale, Expressive One-Word Picture Vocabulary Test-4, and the Clinical Global Impression-Improvement Scale. Structural connectivity was measured at baseline and at 6 months in a subset of 19 children with 25-direction diffusion tensor imaging and deterministic tractography. Behavioral improvements were associated with increased white matter connectivity in frontal, temporal, and subcortical regions (hippocampus and basal ganglia) that have been previously shown to show anatomical, connectivity, and functional abnormalities in ASD. The current results suggest that improvements in social communication skills and a reduction in symptoms in children with ASD following treatment with autologous cord blood infusion were associated with increased structural connectivity in brain networks supporting social, communication, and language abilities. Stem Cells Translational Medicine 2019;8:138&10.