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Objective Recent efforts to tissue engineer long-segment tracheal grafts have been complicated by stenosis and malacia. It has been proposed that both the mechanical characteristics and cell seeding capacity of TETG scaffolds are integral to graft performance. Our aim was to design a tracheal construct that approximates the biomechanical properties of native sheep trachea and optimizes seeding with bone marrow derived mononuclear cells prior to preclinical evaluation in an ovine model. Methods A solution of 8% polyethylene terephthalate (PET) and 3% polyurethane (PU) was prepared at a ratio of either 8:2 or 2:8 and electrospun onto a custom stainless steel mandrel designed to match the dimensional measurements of the juvenile sheep trachea. 3D-printed porous or solid polycarbonate C-shaped rings were embedded within the scaffolds during electrospinning. The scaffolds underwent compression testing in the anterior-posterior and lateral-medial axes and the biomechanical profiles compared to that of a juvenile ovine trachea. The most biomimetic constructs then underwent vacuum seeding with ovine bone marrow derived mononuclear cells. Fluorometric DNA assay was used to quantify scaffold seeding. Results Both porous and solid rings approximated the biomechanics of the native ovine trachea, but the porous rings were most biomimetic. The load-displacement curve of scaffolds fabricated from a ratio of 2:8 PET:PU most closely mimicked that of native trachea in the anterior-posterior and medial-lateral axes. Solid C-ringed scaffolds had a greater cell seeding efficiency when compared to porous ringed scaffolds (Solid: 19 × 104 vs. Porous: 9.6 × 104 cells/mm3, p = 0.0098). Conclusion A long segment tracheal graft composed of 2:8 PET:PU with solid C-rings approximates the biomechanics of the native ovine trachea and demonstrates superior cell seeding capacity of the two prototypes tested. Further preclinical studies using this graft design in vivo would inform the rational design of an optimal TETG scaffold.

Digital health tools and technologies are transforming health care and making significant impacts on how health and care information are collected, used, and shared to achieve best outcomes. As most of the efforts are still focused on clinical settings, the wealth of health information generated outside of clinical settings is not being fully tapped. This is especially true for children with medical complexity (CMC) and their families, as they frequently spend significant hours providing hands-on medical care within the home setting and coordinating activities among multiple providers and other caregivers. In this paper, a multidisciplinary team of stakeholders discusses the value of health information generated at home, how technology can enhance care coordination, and challenges of technology adoption from a patient-centered perspective. Voice interactive technology has been identified to have the potential to transform care coordination for CMC. This paper shares opinions on the promises, limitations, recommended approaches, and challenges of adopting voice technology in health care, especially for the targeted patient population of CMC.

BackgroundNeedles are frequently required for routine medical procedures. Children with severe hemophilia require intensive intravenous (IV) therapy to treat and prevent life-threatening bleeding and undergo hundreds of IV procedures. Fear of needle-related procedures may lead to avoidance of future health care and poor clinical outcomes. Virtual reality (VR) is a promising distraction technique during procedures, but barriers to commercially available VR platforms for pediatric health care purposes have prevented widespread use.ObjectiveWe hypothesized that we could create a VR platform that would be used for pediatric hemophilia care, allow clinician orchestration, and be safe and feasible to use for distraction during IV procedures performed as part of complex health care.MethodsWe created a VR platform comprising wireless, adjustable, disposable headsets and a suite of remotely orchestrated VR games. The platform was customized for a pediatric hemophilia population that required hands-free navigation to allow access to a child’s hands or arms for procedures. A hemophilia nurse observing the procedure performed orchestration. The primary endpoint of the trial was safety. Preliminary feasibility and usability of the platform were assessed in a single-center, randomized clinical trial from June to December 2016. Participants were children with hemophilia aged 6-18 years. After obtaining informed consent, 25 patients were enrolled and randomized. Each subject, 1 caregiver, and 1 hemophilia nurse orchestrator assessed the degree of preprocedural nervousness or anxiety with an anchored, combined modified visual analog (VAS)/FACES scale. Each participant then underwent a timed IV procedure with either VR or standard of care (SOC) distraction. Each rater assessed the distraction methods using the VAS/FACES scale at the completion of the IV procedure, with questions targeting usability, engagement, impact on procedural anxiety, impact on procedural pain, and likability of the distraction technique. Participants, caregivers, and nurses also rated how much they would like to use VR for future procedures. To compare the length of procedure time between the groups, Mann-Whitney test was used.ResultsOf the 25 enrolled children, 24 were included in the primary analysis. No safety concerns or VR sickness occurred. The median procedure time was 10 (range 1-31) minutes in the VR group and was comparable to 9 (range 3-20) minutes in the SOC group (P=.76). Patients in both the groups reported a positive influence of distraction on procedural anxiety and pain. Overall, in 80% (34/45) of the VR evaluations, children, caregivers, and nurses reported that they would like to use VR for future procedures.ConclusionsWe demonstrated that an orchestrated, VR environment could be developed and safely used during pediatric hemophilia care for distraction during IV interventions. This platform has the potential to improve patient experience during medical procedures.Trial RegistrationClinical Trials.gov NCT03507582; https://clinicaltrials.go...

Background Traumatic brain injury (TBI) poses a significant threat to children’s health. Cognitive rehabilitation for pediatric TBI has the potential to improve the quality of life following the injury. Virtual reality (VR) can provide enriched cognitive training in a life-like but safe environment. However, existing VR applications for pediatric TBIs have primarily focused on physical rehabilitation. Objective This study aims to design and develop an integrative hardware and software VR system to provide rehabilitation of executive functions (EF) for children with TBI, particularly in 3 core EF: inhibitory control, working memory, and cognitive flexibility. Methods The VR training system was developed by an interdisciplinary team with expertise in best practices of VR design, developmental psychology, and pediatric TBI rehabilitation. Pilot usability testing of this novel system was conducted among 10 healthy children and 4 children with TBIs. Results Our VR-based interactive cognitive training system was developed to provide assistive training on core EF following pediatric TBI. Pilot usability testing showed adequate user satisfaction ratings for both the hardware and software components of the VR system. Conclusions This project designed and tested a novel VR-based system for executive function rehabilitation that is specifically adapted to children following TBI.

The process of discovering new drugs has been extremely costly and slow in the last decades despite enormous investment in pharmaceutical research. Drug repurposing enables researchers to speed up the process of discovering other conditions that existing drugs can effectively treat, with low cost and fast FDA approval. Here, we introduce ‘RE:fine Drugs’, a freely available interactive website for integrated search and discovery of drug repurposing candidates from GWAS and PheWAS repurposing datasets constructed using previously reported methods in Nature Biotechnology. ‘RE:fine Drugs’ demonstrates the possibilities to identify and prioritize novelty of candidates for drug repurposing based on the theory of transitive Drug–Gene–Disease triads. This public website provides a starting point for research, industry, clinical and regulatory communities to accelerate the investigation and validation of new therapeutic use of old drugs.Database URL: http://drug-repurposing.nationwidechildrens.org

Integrating three-dimensional printing with the creation of tissue-engineered vascular grafts could provide a readily available, patient-specific, autologous tissue source that could significantly improve outcomes in newborns with congenital heart disease. Here, we present the recent case of a candidate for our tissue-engineered vascular graft clinical trial deemed ineligible due to complex anatomical requirements and consider the application of three-dimensional printing technologies for a patient-specific graft. We 3D-printed a closed-disposable seeding device and validated that it performed equivalently to the traditional open seeding technique using ovine bone marrow–derived mononuclear cells. Next, our candidate’s preoperative imaging was reviewed to propose a patient-specific graft. A seeding apparatus was then designed to accommodate the custom graft and 3D-printed on a commodity fused deposition modeler. This exploratory feasibility study represents an important proof of concept advancing progress toward a rationally designed patient-specific tissue-engineered vascular graft for clinical application.

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