A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex.

BackgroundResearch in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers.MethodsCaregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics.ResultsQualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants.ConclusionThe design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families

Analysis of Early Events during the First Year of Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Phase - Chronic Myeloid Leukemia: A "Campus CML" Study

Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML). However, the rst months of therapy are crucial, as optimal response is dened as the achievement of molecular milestones at 3, 6 and 12 months (mo.) and as many toxicities, also causing a TKI switch, are more frequent in the 1st yea

Out of the Ivory Tower: Generalizing Caregiver-Delivered Interventions for Children with Autism Spectrum Disorder

The objective of the present secondary analysis was to compare two short-term caregiver training interventions or preschool children with autism spectrum disorder (ASD) in the primary outcomes of joint engagement and parent behavior in the context of the home. Participants included 28 caregiver-child dyads who were randomly assigned to receive intervention for three months, either group caregiver education (CEM), or 1:1 individualized caregiver mediated intervention (CMM). Joint engagement and parent behavior was coded from 30-minute home observations at entry, exit, and 3 months post-intervention. The CMM group saw a significant positive treatment effect, with gains in both child-initiated joint engagement and parent behavior ratings. Parent behavior mediated the effect of the individualized intervention on joint engagement. This study is among the first to examine the outcomes of joint engagement and parent behavior in the natural context of the family’s home

Illuminating the neglected end of the spectrum: Identifying subgroups of minimally verbal children with ASD and their differential response to intervention

The past thirty years have seen a proliferation in intervention development and testing for autism spectrum disorders (ASD). As a result, there are evidence-based approaches effective at improving the lives of individuals with ASD and their families. However, these approaches frequently have small effects, largely due to the wide heterogeneity that is characteristic of ASD. As those with ASD have a range of cognitive, social, and language characteristics, one-size-fits-all intervention approaches may not best meet the varied needs of this population. Additionally, little intervention research has included or focused on those most in need of effective interventions: those with little to no language. The present examination consists of three studies with the overall aim to characterize heterogeneity in minimally verbal children with ASD and determine whether response to naturalistic versus structured interventions are different depending on child profile. This aim was achieved via secondary data analysis of three separate minimally verbal intervention samples. All included participants had 30 different words or less but in one sample were school-age and received intervention (naturalistic v. structured) for 6 weeks and in another study were preschool-age and received intervention (naturalistic v. structured) for 6 months. Subgroup profiles identified in Study 1 were used as predictors of intervention response in Studies 2 and 3. Results suggest that minimally verbal children with ASD are heterogeneous and can be characterized based on nonverbal versus verbal measures into subgroups, with patterns that emerge in preschool and persist through early childhood. Furthermore, profile subgroups are suggested to account for much of the variability in response to intervention. In particular, having one word on a naturalistic language sample at entry made a difference in subgroup by intervention interactions. For some of the language outcomes, subgroup by intervention interactions suggest that, at least initially, a more structured intervention approach may be more beneficial for those participants with at least one word and the lowest nonverbal and verbal scores across measures while those children with higher scores across measures may benefit from a more naturalistic approach. Implications for future interventions and details are discussed

Thermal markers arising from changes in the protein component of milk

Classification of heat load applied to milk requires the detection of parameters appropriately related to the intensity of the heat treatment. Current analytical methods based on heat-induced changes in the protein component of milk have been directed either to determine the amount of protein-derived products arised from heat treatments or to evaluate the extent of thermal denaturation of milk proteins. Lately, a new analytical strategy has been developed according to the occurrence of three major whey proteins, namely bovine serum albumin (BSA), beta-lactoglobulin (blg) and alfa-lactalbumin (ala), normally soluble at pH 4.6 in raw milk, in the pH 4.6 insoluble protein fraction recovered from heattreated milk. The results have shown that pH 4.6 insoluble BSA, blg and ala, as detected by ELISA in milk, can be regarded as thermal markers suited for either dairy process control or regulation purposes