Measuring the impact of burn injury on the parent-reported health outcomes of children 1-to-5 years: Item pool development for the Preschool1-5 Life Impact Burn Recovery Evaluation (LIBRE) Profile.

Modern, reliable, and valid outcome measures are essential to understanding the health needs of young children with burn injuries. Burn-specific and age-appropriate legacy assessment tools exist for this population but are hindered by the limitations of existing paper-based instruments. The purpose of this study was to develop item pools comprised of questions appropriate for children aged 1-5 with burn injuries. Item development was based on a framework provided by previous work to develop the Preschool Life Impact Burn Recovery Evaluation (LIBRE) Conceptual Model. The Preschool LIBRE Conceptual Model work established four sub-domains of functioning for children with burns aged 1-5. Item development involved a systematic literature review, a qualitative item review process with clinical experts, and parent cognitive interviews. Four item pools were established: (1) communication and language development; (2) physical functioning; (3) psychological functioning and (4) social functioning for preschool-aged children with burn injuries. We selected and refined candidate items, recall periods, survey instructions, and response option choices through clinical and parental feedback during the qualitative review and cognitive interview processes. Item pools are currently being field-tested as part of the process to calibrate and validate the Preschool1-5 LIBRE Computer Adaptive Test (CAT) Profile.

Geographic Variation in Outcomes After Burn Injury: A Burn Model System National Database Study.

BACKGROUND: Geography is an important yet underexplored factor that may influence the care and outcomes of burn survivors. This study aims to examine the impact of geography on physical and psychosocial function after burn injury. METHODS: Data from the Burn Model Systems National Database (1997-2015) were analyzed. Individuals 18 years and older who were alive at discharge were included. Physical and psychosocial functions were assessed at 6, 12, and 24 months postinjury using the following patient-reported outcome measures: Community Integration Questionnaire, Physical Composite Scale and Mental Composite Scale of the 12-Item Short Form Health Survey, Satisfaction with Appearance Scale, and Satisfaction with Life Scale. Descriptive statistics were generated for demographic and medical data, and mixed regression models were used to assess the impact of geography on long-term outcomes. RESULTS: The study included 469 burn survivors from the Centers for Medicare and Medicaid Services regions 10, 31 from region 8, 477 from region 6, 267 from region 3, and 41 from region 1. Participants differed significantly by region in terms of race/ethnicity, burn size, burn etiology, and acute care length of stay (P < 0.001). In adjusted mixed model regression analyses, scores of all 5 evaluated outcome measures were found to differ significantly by region (P < 0.05). CONCLUSIONS: Several long-term physical and psychosocial outcomes of burn survivors vary significantly by region. This variation is not completely explained by differences in population characteristics. Understanding these geographical differences may improve care for burn survivors and inform future policy and resource allocation.

Measuring the Impact of Burn Injury on the Parent-Reported Health Outcomes of Children 1 to 5 Years: A Conceptual Framework for Development of the Preschool Life Impact Burn Recovery Evaluation Profile CAT.

Due to the rapid developmental growth in preschool-aged children, more precise measurement of the effects of burns on child health outcomes is needed. Expanding upon the Shriners Hospitals for Children/American Burn Association Burn Outcome Questionnaire 0 to 5 (BOQ0-5), we developed a conceptual framework describing domains important in assessing recovery from burn injury among preschool-aged children (1-5 years). We developed a working conceptual framework based on the BOQ0-5, the National Research Council and Institute of Medicine's Model of Child Health, and the World Health Organization's International Classification of Functioning, Disability, and Health for Children and Youth. We iteratively refined our framework based on a literature review, focus groups, interviews, and expert consensus meetings. Data were qualitatively analyzed using methods informed by grounded theory. We reviewed 95 pediatric assessments, conducted two clinician focus groups and six parent interviews, and consulted with 23 clinician experts. Three child health outcome domains emerged from our analysis: symptoms, functioning, and family. The symptoms domain describes parents' perceptions of their child's pain, skin-related discomfort, and fatigue. The functioning domain describes children's physical functioning (gross and fine motor function), psychological functioning (internalizing, externalizing, and dysregulation behavior; trauma; toileting; resilience), communication and language development (receiving and producing meaning), and social functioning (connecting with family/peers, friendships, and play). The family domain describes family psychological and routine functioning outcomes.

Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo.

Safe and effective delivery is required for siRNA and mRNA-based therapeutics to reach their potential. Here, we report on the development of poly(glycoamidoamine) brush nanoparticles as delivery vehicles for siRNA and mRNA. These polymers were capable of significant delivery of siRNA against FVII and mRNA-encoding erythropoietin (EPO) in mice. Importantly, these nanoparticles were well-tolerated at their effective dose based on analysis of tissue histology, systemic cytokine levels, and liver enzyme chemistry. The polymer brush nanoparticles reported here are promising for therapeutic applications.

The ABCs of Burn Care for School-Age Children.

Burn injuries are among the most painful injuries any child can endure. This article explains common sources of burn injuries in student populations, diagnosis and classification of burn injuries, initial burn management, and how to determine when a child needs to be evaluated by a physician.

Discrepancy in Initial Pediatric Burn Estimates and Its Impact on Fluid Resuscitation.

One of the fundamental aspects of initial burn care is the ability to accurately measure the TBSA of injured tissue. Discrepancies between initial estimates of burn size and actual TBSA (determined at the burn unit) have long been reported. These inconsistencies have the potential for unnecessary patient transfer and inappropriate fluid administration which may result in morbidity. In an effort to study these inconsistencies and their impact on initial care, we evaluated the differences between initial TBSA estimates and its impact on fluid resuscitation at an American Burn Association-verified pediatric burn center. A prospective observational study of 50 consecutive burn patients admitted to Shriner's Hospital for Children in Boston, Massachusetts, between October 2011 and April 2012 was performed. Data collected included age, mechanism of burn injury, type of referral center, referring hospital TBSA, and volume of fluid administration as well as admission TBSA and volume of fluid administration. Determination of over or under resuscitation was based on comparing the amount of fluids received at the referral center to that received at the pediatric burn center. A total of 50 patients were admitted during the 7-month study period. The average age was 4.1 years old (25 days-16 years) and the average TBSA was 2.5% (0.25-55%). There were significant differences in the TBSA calculations between referring centers and the pediatric burn center. Overestimation of scald and contact burn size (P < .05) was noted with no difference in flame burn size estimation. Community referrals were more likely than tertiary centers to overestimate TBSA (P < .05 vs P = .29). Overall, 59% of study patients were administered more fluid at the referring hospital than would have been expected by the burn size calculated at our facility. Inconsistencies with the estimation of TBSA burn between referring hospitals and tertiary referral centers remains a problem in pediatric patients and may lead to inappropriate resuscitation. This study highlights the continued need for educational outreach programs and for the provision of novel resources to initial burn providers. Additional support through online resources (eg, Lund-Browder diagram) and remotely assisting providers during their TBSA measurements are potential options which may help to improve the initial care of burn patients.

The use of Google Glass for airway assessment and management.

Currently, information about airway assessment and tracheal intubation is communicated verbally or in writing. Google Glass can record this information in real time with minimal disruption to work flow, using standard operating room lighting.

Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity.

One of the most significant challenges in the development of clinically viable delivery systems for RNA interference therapeutics is to understand how molecular structures influence delivery efficacy. Here, we have synthesized 1,400 degradable lipidoids and evaluate their transfection ability and structure-function activity. We show that lipidoid nanoparticles mediate potent gene knockdown in hepatocytes and immune cell populations on IV administration to mice (siRNA EC50 values as low as 0.01 mg kg(-1)). We identify four necessary and sufficient structural and pKa criteria that robustly predict the ability of nanoparticles to mediate greater than 95% protein silencing in vivo. Because these efficacy criteria can be dictated through chemical design, this discovery could eliminate our dependence on time-consuming and expensive cell culture assays and animal testing. Herein, we identify promising degradable lipidoids and describe new design criteria that reliably predict in vivo siRNA delivery efficacy without any prior biological testing.

In vitro-in vivo translation of lipid nanoparticles for hepatocellular siRNA delivery.

A significant challenge in the development of clinically viable siRNA delivery systems is a lack of in vitro-in vivo translatability: many delivery vehicles that are initially promising in cell culture do not retain efficacy in animals. Despite its importance, little information exists on the predictive nature of in vitro methodologies, most likely due to the cost and time associated with generating in vitro-in vivo data sets. Recently, high-throughput techniques have been developed that have allowed the examination of hundreds of lipid nanoparticle formulations for transfection efficiency in multiple experimental systems. The large resulting data set has allowed the development of correlations between in vitro and characterization data and in vivo efficacy for hepatocellular delivery vehicles. Consistency of formulation technique and the type of cell used for in vitro experiments was found to significantly affect correlations, with primary hepatocytes and HeLa cells yielding the most predictive data. Interestingly, in vitro data acquired using HeLa cells were more predictive of in vivo performance than mouse hepatoma Hepa1-6 cells. Of the characterization parameters, only siRNA entrapment efficiency was partially predictive of in vivo silencing potential, while zeta-potential and, surprisingly, nanoparticle size (when <300 nm) as measured by dynamic light scattering were not. These data provide guiding principles in the development of clinically viable siRNA delivery materials and have the potential to reduce experimental costs while improving the translation of materials into animals.