Using normalization process theory to inform practice: evaluation of a virtual autism training for clinicians

BackgroundThere is growing demand for developmental and behavioral pediatric services including autism evaluation and care management. Clinician trainings have been found to result in an increase of knowledge and attitudes. This study utilizes Normalization Process theory (NPT) to evaluate a clinician training program and its effects on practice.MethodsThe year-long virtual training program about autism screening and care management included didactic portions and case presentations. Focus groups and interviews were conducted with primary care clinicians (n = 10) from community health centers (n = 6) across an urban area five months post-training. Transcripts were deductively coded using NPT to uncover barriers to implementation of autism screening and care, benefits of the training program, and areas for future training.ResultsParticipants were motivated by the benefits of expanding and improving support for autistic patients but noted this effort requires effective collaboration within a complex network of care providers including clinicians, insurance agencies, and therapy providers. Although there were support that participants could provide to families there were still barriers including availability of behavior therapy and insufficient staffing. Overall, participants positively viewed the training and reported implementing new strategies into practice.ConclusionDespite the small sample size, application of NPT allowed for assessment of both training delivery and implementation of strategies, and identification of recommendations for future training and practice sustainability. Follow-up focus groups explored participants' practice five months post-program. Variations in participants' baseline experience and context at follow-up to enable application of skills should be considered when using NPT to evaluate clinician trainings

Gene therapy for the treatment of Niemann-Pick disease type C1: Comparison of AAV9 to a novel serotype, AAV-PHP.B

[no abstract

Gene therapy for the treatment of Niemann-Pick disease type C1: Comparison of AAV9 to a novel serotype, AAV-PHP.B

[no abstract

Enhanced Efficacy of Gene Therapy Treatment for Niemann-Pick C1 Disease Using a Novel Serotype, AAV-PHP.B

Accessing the central nervous system (CNS) continues to present a challenge when developing therapies for the treatment of neurological diseases. Overcoming the barrier of gene transfer to brains of animals and patients from systemic circulation has been difficult. Recent advances using Cre recombination-based adeno-associated virus (AAV) targeted evolution (CREATE) has yielded a promising new serotype, AAV-PHP.B, with greater transduction than AAV9 in the adult mouse CNS after systemic delivery. Here we show systemic delivery of a therapeutic AAV-PHP.B vector outperforms the naturally occurring AAV9 in treatment of a murine model of a rare lysosomal storage disorder, Niemann-Pick C1 (NPC1) disease. Approximately 95% of patients have a mutation in NPC1 which results in either absence or a significant reduction in functional NPC1, a lysosomal transmembrane protein involved in cholesterol transport. NPC1 pathology involves lysosomal accumulation of unesterified cholesterol and other lipids. Patients typically present with neurological symptoms and visceral complications including hepatosplenomegaly. Disease progression in the null mouse model of NPC1 (Npc1-/-) is characterized by weight loss, ataxia, and early death. Results: We previously reported that systemic delivery of an AAV9 vector expressing the human NPC1 gene under transcriptional control of a ubiquitous promoter (EF1a) improved lifespan and ameliorated disease phenotype of Npc1-/- mice. Using a similar study design, we find that an otherwise identical AAV-PHP.B vector improved lifespan in Npc1-/- mice more effectively than an AAV9 vector